中华中医药学刊

组别	n	ATP	ADP	AMP
正常组	5	2.136±0.114	2.529±0.125	4.298（0.218）
模型组	5	0.878±0.145^a	6.033±0.344^a	11.430（1.634）^a
三七低剂量组	5	1.015±0.095^a	4.835±0.296^ab	9.272（0.735）^ab
三七中剂量组	5	1.279±0.117^ab	4.435±0.272^ab	8.287（0.120）^ab
三七高剂量组	5	1.882±0.154^ab	2.889±0.253^ab	4.707（0.347）^b
阳性对照组	5	1.896±0.176^ab	3.411±0.243^ab	5.834（0.411）^ab
F值/H值		74.017	125.381	27.126
P值		0.000	0.000	0.000

组别	n	ATP	ADP	AMP
正常组	5	2.136±0.114	2.529±0.125	4.298（0.218）
模型组	5	0.878±0.145^a	6.033±0.344^a	11.430（1.634）^a
三七低剂量组	5	1.015±0.095^a	4.835±0.296^ab	9.272（0.735）^ab
三七中剂量组	5	1.279±0.117^ab	4.435±0.272^ab	8.287（0.120）^ab
三七高剂量组	5	1.882±0.154^ab	2.889±0.253^ab	4.707（0.347）^b
阳性对照组	5	1.896±0.176^ab	3.411±0.243^ab	5.834（0.411）^ab
F值/H值		74.017	125.381	27.126
P值		0.000	0.000	0.000

组别	n	Na⁺-K⁺-ATP酶活性	Ca²⁺-Mg²⁺-ATP酶活性
正常组	5	5.838±0.281	3.314±0.092
模型组	5	2.561±0.133^a	1.261±0.106^a
三七低剂量组	5	3.132±0.175^ab	1.682±0.138^ab
三七中剂量组	5	3.722±0.188^ab	2.269±0.229^ab
三七高剂量组	5	4.771±0.275^ab	2.679±0.238^ab
阳性对照组	5	4.649±0.379^ab	2.762±0.240^ab
F值		113.655	82.937
P值		0.000	0.000

组别	n	Na⁺-K⁺-ATP酶活性	Ca²⁺-Mg²⁺-ATP酶活性
正常组	5	5.838±0.281	3.314±0.092
模型组	5	2.561±0.133^a	1.261±0.106^a
三七低剂量组	5	3.132±0.175^ab	1.682±0.138^ab
三七中剂量组	5	3.722±0.188^ab	2.269±0.229^ab
三七高剂量组	5	4.771±0.275^ab	2.679±0.238^ab
阳性对照组	5	4.649±0.379^ab	2.762±0.240^ab
F值		113.655	82.937
P值		0.000	0.000

组别	n	Ⅰ	Ⅱ	Ⅲ	Ⅳ
正常组	5	51.533±3.797	9.612（0.421）	12.720±1.003	13.157（1.878）
模型组	5	17.071±3.012^a	4.411（0.558）^a	3.902±0.233^a	5.205（1.234）^a
三七低剂量组	5	19.549±5.123^a	5.13（0.548）^ab	5.259±0.812^ab	5.239（1.582）^a
三七中剂量组	5	30.985±4.925^ab	5.47（0.459）^ab	7.311±1.015^ab	8.093（1.832）^ab
三七高剂量组	5	43.437±4.977^ab	7.896（3.096）^b	9.482±0.879^ab	10.702（1.811）^ab
阳性对照组	5	41.220±1.999^ab	7.425（3.649）^b	9.495±0.650^ab	9.640（0.287）^ab
F值/χ²值		55.647	22.492	78.314	26.079
P值		0.000	0.000	0.000	0.000

组别	n	Ⅰ	Ⅱ	Ⅲ	Ⅳ
正常组	5	51.533±3.797	9.612（0.421）	12.720±1.003	13.157（1.878）
模型组	5	17.071±3.012^a	4.411（0.558）^a	3.902±0.233^a	5.205（1.234）^a
三七低剂量组	5	19.549±5.123^a	5.13（0.548）^ab	5.259±0.812^ab	5.239（1.582）^a
三七中剂量组	5	30.985±4.925^ab	5.47（0.459）^ab	7.311±1.015^ab	8.093（1.832）^ab
三七高剂量组	5	43.437±4.977^ab	7.896（3.096）^b	9.482±0.879^ab	10.702（1.811）^ab
阳性对照组	5	41.220±1.999^ab	7.425（3.649）^b	9.495±0.650^ab	9.640（0.287）^ab
F值/χ²值		55.647	22.492	78.314	26.079
P值		0.000	0.000	0.000	0.000

名称	mz	rt	P .value	VIP	Model	LD	MD	HD
N-Methyl-2-pyrrolidinone	100.075 9	350.6	0.019 3	1.049 8	no change	no change	no change	no change
1-Aminocyclopropanecarboxylic acid	102.055 2	159.4	0.000 0	1.353 8	down	no change	up	no change
2-Phenylethanol	105.069 6	381.9	0.024 2	2.164 8	no change	no change	no change	up
Imidazole-4-acetaldehyde	111.055 1	121.1	0.012 0	2.388 3	up	no change	no change	up
Histamine	112.086 7	74.6	0.011 7	1.105 4	no change	no change	up	no change
Purine	120.044 2	694.3	0.006 1	2.348 1	up	up	no change	no change
Maltol	127.038 5	231.2	0.000 0	1.467 1	no change	up	no change	no change
（S）-2，3，4，5-tetrahydropyridine-2-carboxylate	128.070 3	341.5	0.000 7	1.234 4	no change	no change	no change	no change
5-Hydroxymethylfurfuryl alcohol	128.049 4	673.7	0.034 4	2.835 0	no change	down	down	down
Octanal	129.127 2	596.8	0.005 2	1.128 8	down	no change	no change	no change
5-Amino-2-oxopentanoic acid	131.070 0	199.0	0.027 2	2.152 7	no change	no change	no change	down
N-Acetyl-beta-alanine	132.065 0	162.3	0.047 5	1.792 8	up	up	no change	no change
1，3-Dihydro-（2H）-indol-2-one	134.059 9	452.4	0.002 3	1.407 2	no change	up	up	no change
Phosphonoacetate	140.070 4	299.7	0.034 9	2.038 5	up	no change	no change	up
Valpromide	144.137 9	474.4	0.018 8	2.297 4	no change	up	no change	no change
Acetylcholine	146.117 2	96.7	0.023 4	1.598 0	up	up	no change	up
O-Acetylserine	148.060 1	159.2	0.030 2	1.583 3	no change	down	no change	no change
Cuminaldehyde	149.095 8	488.1	0.012 0	1.704 1	down	down	no change	down
D-Arabitol	152.070 3	432.7	0.000 2	1.720 7	down	no change	down	down
Protocatechuic acid	155.106 4	537.4	0.013 6	1.700 3	no change	down	no change	no change
Tranexamic Acid	158.117 3	414.6	0.004 5	1.910 3	down	no change	down	down
D-Alanyl-D-alanine	160.096 6	442.1	0.008 5	1.166 0	up	no change	up	up
4-Hydroxy-2-quinolone	161.046 8	476.7	0.003 1	1.887 7	up	up	no change	no change
N-methyl-L-glutamic Acid	161.070 7	502.1	0.032 2	1.247 6	up	no change	no change	no change
Anabasine	163.038 7	591.9	0.004 1	1.874 3	no change	down	no change	no change
Isosafrole	163.075 2	868.4	0.003 4	1.661 0	up	up	up	up
Enol-phenylpyruvate	165.054 3	310.7	0.003 0	1.845 7	up	no change	up	up
4-Phenylbutyrate	165.090 6	545.7	0.001 8	1.166 5	no change	up	no change	no change
Epinephrine	166.086 2	377.7	0.000 2	1.499 5	no c hange	up	up	up
Desaminotyrosine	167.073 9	164.6	0.032 3	1.352 5	up	up	up	no change
Tropate	167.081 3	425.3	0.001 7	1.504 5	no change	up	up	no change
Perillic acid	167.106 1	617.9	0.002 2	1.505 2	no change	no change	down	no change
Quinolinic acid	167.012 6	74.7	0.003 0	1.479 4	no change	no change	no change	no change
Isopyridoxal	168.065 1	197.4	0.046 2	1.597 0	no change	no change	up	no change
Pyridoxamine	169.097 1	269.8	0.013 9	1.421 1	no change	no change	no change	no change
2-Biphenylol	171.076 4	298.5	0.001 3	1.137 9	down	no change	down	down
Iminoarginine	172.107 8	210.5	0.045 4	1.333 9	no change	no change	up	no change
Swainsonine	174.112 1	350.0	0.019 2	1.444 0	down	no change	no change	no change
Formiminoglutamic acid	175.071 0	101.7	0.023 0	1.512 9	no change	no change	no change	no change
1 H-Indole-3-acetamide	175.086 4	503.2	0.043 1	1.929 3	down	no change	no change	down
3-Methyl-L-tyrosine	178.086 1	325.5	0.006 0	2.552 8	no change	no change	no change	up
Methyleugenolu	179.106 4	792.0	0.002 0	1.352 7	up	no change	no change	up
5-Oxo-1，2-campholide	183.101 2	612.8	0.012 3	1.165 2	up	up	no change	no change
Sebacic acid	185.117 5	528.6	0.042 7	2.034 5	up	no change	no change	up
Deethylatrazine	188.070 3	673.5	0.022 0	2.026 3	up	up	up	up
Methyl（indol-3-yl）acetate	189.078 3	649.5	0.024 6	2.096 0	no change	no change	no change	up
Myristicin	193.085 4	515.9	0.002 3	2.131 1	up	no change	no change	up
Methoxamine	194.117 4	217.6	0.025 6	2.140 0	down	no change	no change	down
3，4-Methylenedioxyamphetamine	194.117 0	313.1	0.002 1	2.791 8	no change	no change	no change	down
（-）-Bornesitol	194.081 0	512.0	0.001 6	1.231 4	up	up	up	no change
Dopaquinone	196.059 9	375.3	0.043 0	1.788 0	no change	down	down	down
Dethiobiotin	197.127 9	209.0	0.000 3	1.345 3	up	up	up	up
N-Acetylhistidine	198.086 6	100.4	0.033 5	1.392 9	down	no change	no change	no change
Spermine	203.222 5	77.4	0.002 9	1.089 6	no change	no change	no change	no change
Bufotenin	205.137 2	177.1	0.015 4	1.260 8	no change	down	no change	no change
trans-Isoasarone	209.116 8	490.0	0.014 2	1.417 9	no change	up	no change	no change
Propoxur	210.112 3	467.3	0.005 9	2.200 1	up	up	up	up
（+）-7-Isojasmonic acid	211.132 4	481.2	0.000 1	1.072 9	up	up	up	up
3-Methyl-1-（2，4，6-trihydroxyphenyl）-1-butanone	211.096 0	515.9	0.031 2	2.018 0	no change	no change	no change	up
Apiole	223.095 4	570.2	0.005 7	1.875 3	up	up	up	no change
Terbutaline	226.143 1	651.6	0.007 8	2.487 9	no change	down	down	down
Pirbuterol	241.153 9	128.0	0.000 1	1.774 1	up	no change	up	no change
Ribavirin	244.078 6	96.9	0.003 4	1.272 0	up	no change	no change	down
Biotin	245.094 9	461.3	0.001 7	1.297 4	down	no change	no change	no change
Osthol	245.116 5	716.3	0.000 1	1.671 2	up	no change	up	no change
N-Acetyl-D-tryptophan	247.128 3	377.2	0.015 3	2.368 8	no change	no change	no change	up
D-Octopine	247.139 1	96.8	0.004 1	2.145 9	up	no change	no change	up
5-Hydroxyindoleacetylglycine	249.086 4	515.1	0.016 6	2.172 1	no change	no change	up	up
Citrinin	251.090 7	605.2	0.000 4	1.329 6	up	no change	up	up
16-Oxopalmitate	253.215 4	705.9	0.002 3	1.894 7	no change	down	no change	no change
16-Hydroxy hexadecanoic acid	255.230 8	844.2	0.036 8	1.898 8	no change	no change	no change	no change
Stearolic acid	263.236 2	868.1	0.000 8	2.952 8	down	down	down	down
gamma-Glutamyltyramine	266.120 7	454.9	0.000 0	1.732 3	up	up	up	up
Nevirapine	267.120 0	488.9	0.001 2	1.761 9	no change	up	up	up
Xanthoxic acid	267.162 8	667.4	0.043 1	1.620 8	no change	no change	no change	no change
Baicalein	271.179 7	702.9	0.000 0	1.909 4	no change	no change	up	no change
（5-L-Glutamyl）-L-glutamate	277.103 7	131.7	0.000 1	1.341 7	up	up	up	up
Sulfamethazine	279.092 6	749.0	0.040 8	1.030 1	no change	no change	no change	no change
Guanosine	284.098 4	280.3	0.034 0	1.141 6	no change	no change	no change	no change
9-OxoODE	295.225 6	867.6	0.008 8	2.429 9	up	up	no change	up
Enterolactone	299.126 8	594.6	0.002 1	1.547 7	up	no change	up	up
Dihydrocapsaicin	308.220 7	626.3	0.000 1	2.735 5	up	up	up	up
Moupinamide	314.123 7	174.4	0.019 1	1.143 0	down	no change	no change	no change
N-Acetylthienamycin	314.102 6	76.8	0.038 8	1.170 4	no change	no change	down	no change
Oxycodone	316.154 1	510.0	0.027 2	1.497 7	up	up	up	no change
Clostebol	323.182 7	653.5	0.004 4	1.738 5	no cha nge	no change	up	no change
Melibiose	325.112 6	322.2	0.015 2	2.389 3	no cha nge	no change	no change	no change
Bitertanol	338.194 7	732.1	0.001 0	2.094 7	no change	down	no change	no change
17alpha，21-Dihydroxypregnenolone	349.235 9	563.2	0.012 0	1.706 2	no change	no change	no change	no change
Cortisone	360.202 7	450.8	0.004 1	1.179 6	up	up	up	no change
Aldosterone	361.220 4	877.6	0.035 6	1.759 6	no change	no change	no change	no change
18-Hydroxycorticosterone	363.214 7	546.5	0.023 3	1.170 0	no change	no change	no change	down
Tangeritin	373.127 5	794.1	0.000 0	1.097 4	down	no change	down	down
S-Adenosylmethionine	398.239 8	792.9	0.016 6	1.347 2	no change	no change	no change	no change
N1，N8-Bis（4-coumaroyl）spermidine	438.240 2	489.8	0.003 8	1.191 6	down	no change	no change	down
Creatinine	112.984 7	921.7	0.011 9	2.422 1	no change	no change	no change	up
5-Aminopentanoic acid	115.920 9	813.7	0.017 1	1.614 0	no change	no change	down	down
Citramalic acid	129.018 8	142.0	0.001 0	1.893 8	down	no change	down	down
Glycyl-glycine	132.048 9	177.9	0.034 7	1.877 3	no change	no change	no change	down
Adenine	134.047 4	250.6	0.034 4	1.943 5	no change	no change	no change	no change
3-Dehydro-L-threonate	134.024 9	452.7	0.001 3	1.297 0	down	no change	down	down
Threonic acid	135.030 1	118.1	0.043 1	1.451 5	no change	no change	no change	no change
Dimethylbenzimidazole	145.040 8	431.2	0.005 8	2.076 3	no change	no change	no change	no change
D-Glutamine	145.062 2	88.5	0.017 8	1.212 3	no change	no change	no change	no change
3-Aminopentanedioate	146.046 0	94.3	0.000 9	1.252 4	up	no change	no change	no change
6-Methyladenine	148.063 0	350.2	0.009 5	1.673 5	up	no change	no change	up
D-Xylose	149.045 7	93.0	0.015 5	1.286 7	up	no change	no change	up
（R）-Mandelamide	151.060 6	983.4	0.011 8	1.356 9	no change	down	no change	no change
3-Hydroxyvalproic acid	159.102 6	331.4	0.030 8	1.513 1	no change	no change	no change	no change
Oxoadipic acid	160.040 6	454.3	0.022 4	2.288 4	no change	no change	no change	up
Umbelliferone	161.024 5	533.1	0.048 6	2.446 7	no change	no change	no change	no change
L-Phenylalanine	164.071 8	304.9	0.008 4	1.220 6	no change	no change	no change	up
6-Methylmercaptopurine	165.021 0	142.5	0.001 0	1.642 3	up	up	no change	no change
Terephthalate	165.019 7	388.4	0.022 1	1.642 2	no change	no change	no change	up
Hydantoin-5-propionic acid	171.041 4	95.7	0.018 2	1.498 5	up	no change	no change	no change
N-Acetylleucine	172.098 0	340.4	0.017 4	1.108 7	no change	no change	no change	up
Allantoic acid	175.048 3	82.7	0.000 1	1.035 9	down	no change	no change	no change
2-Dehydro-D-glucono-1，5-lactone	176.035 3	206.6	0.001 2	1.209 1	no change	down	no change	no change
D-Mannonate	177.040 5	81.4	0.002 7	1.195 3	no change	down	no change	no change
4-Hydroxyphenylpyruvic acid	179.035 2	303.3	0.000 4	1.048 9	no change	no change	no change	no change
D-Mannose	179.056 4	90.1	0.012 9	1.120 3	no change	no change	up	no change
Homovanillate	181.050 7	164.0	0.021 2	2.061 9	up	up	no change	no change
Hydroxyphenyllactic acid	181.050 5	253.8	0.000 0	2.968 4	no change	up	up	up
2＇，6＇-Dihydroxy-4＇-methoxyacetophenone	181.050 6	426.9	0.033 6	1.037 9	up	no change	up	no change
10-Oxodecanoate	186.121 9	459.7	0.003 8	1.003 1	no change	down	no change	no change
trans-Ferulic acid	193.050 8	296.6	0.000 1	1.614 6	down	down	down	down
Galactaric acid	209.030 2	77.5	0.001 7	1.450 4	up	no change	no change	no change
Milrinone	210.067 1	609.4	0.004 5	1.762 7	no change	no change	no change	no change
Tridecanoic acid	214.108 6	393.8	0.050 0	2.001 8	no change	no change	no change	down
N-Acetyl-D-glucosamine	221.154 8	855.3	0.010 5	1.773 0	no change	no change	no change	no change
Aciclovir	225.080 3	425.4	0.006 0	1.062 3	down	no change	down	down
Xylitol 5-phosphate	231.027 7	100.4	0.024 8	1.257 3	up	no change	up	no change
Equol	241.087 2	685.9	0.003 2	1.631 0	no change	down	no change	no change
Uridine	243.061 8	166.7	0.019 9	2.366 6	down	down	no change	no change
Pyridoxal phosphate	247.028 0	317.9	0.011 7	1.148 0	up	no change	no change	no change
Shikimate 3-phosphate	253.017 8	470.8	0.003 9	2.324 5	no change	no change	no change	down
Palmitic acid	255.233 1	874.8	0.002 3	1.503 0	up	no change	no change	no change
Zidovudine	267.090 7	459.3	0.000 0	1.243 5	up	up	up	up
Norizalpinin	269.045 6	471.3	0.013 3	1.542 7	no change	no change	down	no change
3＇-Hydroxydaidzein	269.045 5	537.3	0.011 1	1.040 4	no change	no change	no change	no change
Arbutin	272.095 7	569.0	0.004 3	2.042 9	down	no change	no change	down
beta-D-3-Ribofuranosyluric acid	281.053 9	128.2	0.021 9	1.251 5	no change	no change	no change	no change
Dihydrotestosterone	289.165 9	322.0	0.000 0	1.042 4	up	no change	up	up
Kaempferide	299.056 3	687.9	0.000 1	1.744 2	up	n o change	no change	no change
Morin	301.037 7	369.6	0.036 2	1.052 9	down	no change	no change	no change
（S，E）-Zearalenone	317.139 2	787.7	0.001 7	2.381 2	no change	no change	no change	no change
GMP	344.039 7	149.6	0.001 8	1.044 0	no change	up	no change	down
Pirenzepine	350.163 4	521.1	0.000 0	1.605 7	up	no change	up	down
Sinigrin	359.033 7	419.2	0.000 0	2.481 8	no change	up	no change	up
Deoxycholic acid	392.288 1	790.8	0.019 7	1.005 2	no change	no change	no change	no change
Carvedilol	405.189 0	563.4	0.021 2	1.369 0	down	down	no change	no change
Allocholic acid	407.281 7	677.7	0.031 1	1.169 0	down	down	down	no change
Daidzin	415.101 5	491.3	0.040 8	1.823 3	no change	no change	no change	no change
Astragalin	448.108 5	464.7	0.028 8	2.674 4	no ch ange	no change	no change	no change

名称	mz	rt	P .value	VIP	Model	LD	MD	HD
N-Methyl-2-pyrrolidinone	100.075 9	350.6	0.019 3	1.049 8	no change	no change	no change	no change
1-Aminocyclopropanecarboxylic acid	102.055 2	159.4	0.000 0	1.353 8	down	no change	up	no change
2-Phenylethanol	105.069 6	381.9	0.024 2	2.164 8	no change	no change	no change	up
Imidazole-4-acetaldehyde	111.055 1	121.1	0.012 0	2.388 3	up	no change	no change	up
Histamine	112.086 7	74.6	0.011 7	1.105 4	no change	no change	up	no change
Purine	120.044 2	694.3	0.006 1	2.348 1	up	up	no change	no change
Maltol	127.038 5	231.2	0.000 0	1.467 1	no change	up	no change	no change
（S）-2，3，4，5-tetrahydropyridine-2-carboxylate	128.070 3	341.5	0.000 7	1.234 4	no change	no change	no change	no change
5-Hydroxymethylfurfuryl alcohol	128.049 4	673.7	0.034 4	2.835 0	no change	down	down	down
Octanal	129.127 2	596.8	0.005 2	1.128 8	down	no change	no change	no change
5-Amino-2-oxopentanoic acid	131.070 0	199.0	0.027 2	2.152 7	no change	no change	no change	down
N-Acetyl-beta-alanine	132.065 0	162.3	0.047 5	1.792 8	up	up	no change	no change
1，3-Dihydro-（2H）-indol-2-one	134.059 9	452.4	0.002 3	1.407 2	no change	up	up	no change
Phosphonoacetate	140.070 4	299.7	0.034 9	2.038 5	up	no change	no change	up
Valpromide	144.137 9	474.4	0.018 8	2.297 4	no change	up	no change	no change
Acetylcholine	146.117 2	96.7	0.023 4	1.598 0	up	up	no change	up
O-Acetylserine	148.060 1	159.2	0.030 2	1.583 3	no change	down	no change	no change
Cuminaldehyde	149.095 8	488.1	0.012 0	1.704 1	down	down	no change	down
D-Arabitol	152.070 3	432.7	0.000 2	1.720 7	down	no change	down	down
Protocatechuic acid	155.106 4	537.4	0.013 6	1.700 3	no change	down	no change	no change
Tranexamic Acid	158.117 3	414.6	0.004 5	1.910 3	down	no change	down	down
D-Alanyl-D-alanine	160.096 6	442.1	0.008 5	1.166 0	up	no change	up	up
4-Hydroxy-2-quinolone	161.046 8	476.7	0.003 1	1.887 7	up	up	no change	no change
N-methyl-L-glutamic Acid	161.070 7	502.1	0.032 2	1.247 6	up	no change	no change	no change
Anabasine	163.038 7	591.9	0.004 1	1.874 3	no change	down	no change	no change
Isosafrole	163.075 2	868.4	0.003 4	1.661 0	up	up	up	up
Enol-phenylpyruvate	165.054 3	310.7	0.003 0	1.845 7	up	no change	up	up
4-Phenylbutyrate	165.090 6	545.7	0.001 8	1.166 5	no change	up	no change	no change
Epinephrine	166.086 2	377.7	0.000 2	1.499 5	no c hange	up	up	up
Desaminotyrosine	167.073 9	164.6	0.032 3	1.352 5	up	up	up	no change
Tropate	167.081 3	425.3	0.001 7	1.504 5	no change	up	up	no change
Perillic acid	167.106 1	617.9	0.002 2	1.505 2	no change	no change	down	no change
Quinolinic acid	167.012 6	74.7	0.003 0	1.479 4	no change	no change	no change	no change
Isopyridoxal	168.065 1	197.4	0.046 2	1.597 0	no change	no change	up	no change
Pyridoxamine	169.097 1	269.8	0.013 9	1.421 1	no change	no change	no change	no change
2-Biphenylol	171.076 4	298.5	0.001 3	1.137 9	down	no change	down	down
Iminoarginine	172.107 8	210.5	0.045 4	1.333 9	no change	no change	up	no change
Swainsonine	174.112 1	350.0	0.019 2	1.444 0	down	no change	no change	no change
Formiminoglutamic acid	175.071 0	101.7	0.023 0	1.512 9	no change	no change	no change	no change
1 H-Indole-3-acetamide	175.086 4	503.2	0.043 1	1.929 3	down	no change	no change	down
3-Methyl-L-tyrosine	178.086 1	325.5	0.006 0	2.552 8	no change	no change	no change	up
Methyleugenolu	179.106 4	792.0	0.002 0	1.352 7	up	no change	no change	up
5-Oxo-1，2-campholide	183.101 2	612.8	0.012 3	1.165 2	up	up	no change	no change
Sebacic acid	185.117 5	528.6	0.042 7	2.034 5	up	no change	no change	up
Deethylatrazine	188.070 3	673.5	0.022 0	2.026 3	up	up	up	up
Methyl（indol-3-yl）acetate	189.078 3	649.5	0.024 6	2.096 0	no change	no change	no change	up
Myristicin	193.085 4	515.9	0.002 3	2.131 1	up	no change	no change	up
Methoxamine	194.117 4	217.6	0.025 6	2.140 0	down	no change	no change	down
3，4-Methylenedioxyamphetamine	194.117 0	313.1	0.002 1	2.791 8	no change	no change	no change	down
（-）-Bornesitol	194.081 0	512.0	0.001 6	1.231 4	up	up	up	no change
Dopaquinone	196.059 9	375.3	0.043 0	1.788 0	no change	down	down	down
Dethiobiotin	197.127 9	209.0	0.000 3	1.345 3	up	up	up	up
N-Acetylhistidine	198.086 6	100.4	0.033 5	1.392 9	down	no change	no change	no change
Spermine	203.222 5	77.4	0.002 9	1.089 6	no change	no change	no change	no change
Bufotenin	205.137 2	177.1	0.015 4	1.260 8	no change	down	no change	no change
trans-Isoasarone	209.116 8	490.0	0.014 2	1.417 9	no change	up	no change	no change
Propoxur	210.112 3	467.3	0.005 9	2.200 1	up	up	up	up
（+）-7-Isojasmonic acid	211.132 4	481.2	0.000 1	1.072 9	up	up	up	up
3-Methyl-1-（2，4，6-trihydroxyphenyl）-1-butanone	211.096 0	515.9	0.031 2	2.018 0	no change	no change	no change	up
Apiole	223.095 4	570.2	0.005 7	1.875 3	up	up	up	no change
Terbutaline	226.143 1	651.6	0.007 8	2.487 9	no change	down	down	down
Pirbuterol	241.153 9	128.0	0.000 1	1.774 1	up	no change	up	no change
Ribavirin	244.078 6	96.9	0.003 4	1.272 0	up	no change	no change	down
Biotin	245.094 9	461.3	0.001 7	1.297 4	down	no change	no change	no change
Osthol	245.116 5	716.3	0.000 1	1.671 2	up	no change	up	no change
N-Acetyl-D-tryptophan	247.128 3	377.2	0.015 3	2.368 8	no change	no change	no change	up
D-Octopine	247.139 1	96.8	0.004 1	2.145 9	up	no change	no change	up
5-Hydroxyindoleacetylglycine	249.086 4	515.1	0.016 6	2.172 1	no change	no change	up	up
Citrinin	251.090 7	605.2	0.000 4	1.329 6	up	no change	up	up
16-Oxopalmitate	253.215 4	705.9	0.002 3	1.894 7	no change	down	no change	no change
16-Hydroxy hexadecanoic acid	255.230 8	844.2	0.036 8	1.898 8	no change	no change	no change	no change
Stearolic acid	263.236 2	868.1	0.000 8	2.952 8	down	down	down	down
gamma-Glutamyltyramine	266.120 7	454.9	0.000 0	1.732 3	up	up	up	up
Nevirapine	267.120 0	488.9	0.001 2	1.761 9	no change	up	up	up
Xanthoxic acid	267.162 8	667.4	0.043 1	1.620 8	no change	no change	no change	no change
Baicalein	271.179 7	702.9	0.000 0	1.909 4	no change	no change	up	no change
（5-L-Glutamyl）-L-glutamate	277.103 7	131.7	0.000 1	1.341 7	up	up	up	up
Sulfamethazine	279.092 6	749.0	0.040 8	1.030 1	no change	no change	no change	no change
Guanosine	284.098 4	280.3	0.034 0	1.141 6	no change	no change	no change	no change
9-OxoODE	295.225 6	867.6	0.008 8	2.429 9	up	up	no change	up
Enterolactone	299.126 8	594.6	0.002 1	1.547 7	up	no change	up	up
Dihydrocapsaicin	308.220 7	626.3	0.000 1	2.735 5	up	up	up	up
Moupinamide	314.123 7	174.4	0.019 1	1.143 0	down	no change	no change	no change
N-Acetylthienamycin	314.102 6	76.8	0.038 8	1.170 4	no change	no change	down	no change
Oxycodone	316.154 1	510.0	0.027 2	1.497 7	up	up	up	no change
Clostebol	323.182 7	653.5	0.004 4	1.738 5	no cha nge	no change	up	no change
Melibiose	325.112 6	322.2	0.015 2	2.389 3	no cha nge	no change	no change	no change
Bitertanol	338.194 7	732.1	0.001 0	2.094 7	no change	down	no change	no change
17alpha，21-Dihydroxypregnenolone	349.235 9	563.2	0.012 0	1.706 2	no change	no change	no change	no change
Cortisone	360.202 7	450.8	0.004 1	1.179 6	up	up	up	no change
Aldosterone	361.220 4	877.6	0.035 6	1.759 6	no change	no change	no change	no change
18-Hydroxycorticosterone	363.214 7	546.5	0.023 3	1.170 0	no change	no change	no change	down
Tangeritin	373.127 5	794.1	0.000 0	1.097 4	down	no change	down	down
S-Adenosylmethionine	398.239 8	792.9	0.016 6	1.347 2	no change	no change	no change	no change
N1，N8-Bis（4-coumaroyl）spermidine	438.240 2	489.8	0.003 8	1.191 6	down	no change	no change	down
Creatinine	112.984 7	921.7	0.011 9	2.422 1	no change	no change	no change	up
5-Aminopentanoic acid	115.920 9	813.7	0.017 1	1.614 0	no change	no change	down	down
Citramalic acid	129.018 8	142.0	0.001 0	1.893 8	down	no change	down	down
Glycyl-glycine	132.048 9	177.9	0.034 7	1.877 3	no change	no change	no change	down
Adenine	134.047 4	250.6	0.034 4	1.943 5	no change	no change	no change	no change
3-Dehydro-L-threonate	134.024 9	452.7	0.001 3	1.297 0	down	no change	down	down
Threonic acid	135.030 1	118.1	0.043 1	1.451 5	no change	no change	no change	no change
Dimethylbenzimidazole	145.040 8	431.2	0.005 8	2.076 3	no change	no change	no change	no change
D-Glutamine	145.062 2	88.5	0.017 8	1.212 3	no change	no change	no change	no change
3-Aminopentanedioate	146.046 0	94.3	0.000 9	1.252 4	up	no change	no change	no change
6-Methyladenine	148.063 0	350.2	0.009 5	1.673 5	up	no change	no change	up
D-Xylose	149.045 7	93.0	0.015 5	1.286 7	up	no change	no change	up
（R）-Mandelamide	151.060 6	983.4	0.011 8	1.356 9	no change	down	no change	no change
3-Hydroxyvalproic acid	159.102 6	331.4	0.030 8	1.513 1	no change	no change	no change	no change
Oxoadipic acid	160.040 6	454.3	0.022 4	2.288 4	no change	no change	no change	up
Umbelliferone	161.024 5	533.1	0.048 6	2.446 7	no change	no change	no change	no change
L-Phenylalanine	164.071 8	304.9	0.008 4	1.220 6	no change	no change	no change	up
6-Methylmercaptopurine	165.021 0	142.5	0.001 0	1.642 3	up	up	no change	no change
Terephthalate	165.019 7	388.4	0.022 1	1.642 2	no change	no change	no change	up
Hydantoin-5-propionic acid	171.041 4	95.7	0.018 2	1.498 5	up	no change	no change	no change
N-Acetylleucine	172.098 0	340.4	0.017 4	1.108 7	no change	no change	no change	up
Allantoic acid	175.048 3	82.7	0.000 1	1.035 9	down	no change	no change	no change
2-Dehydro-D-glucono-1，5-lactone	176.035 3	206.6	0.001 2	1.209 1	no change	down	no change	no change
D-Mannonate	177.040 5	81.4	0.002 7	1.195 3	no change	down	no change	no change
4-Hydroxyphenylpyruvic acid	179.035 2	303.3	0.000 4	1.048 9	no change	no change	no change	no change
D-Mannose	179.056 4	90.1	0.012 9	1.120 3	no change	no change	up	no change
Homovanillate	181.050 7	164.0	0.021 2	2.061 9	up	up	no change	no change
Hydroxyphenyllactic acid	181.050 5	253.8	0.000 0	2.968 4	no change	up	up	up
2＇，6＇-Dihydroxy-4＇-methoxyacetophenone	181.050 6	426.9	0.033 6	1.037 9	up	no change	up	no change
10-Oxodecanoate	186.121 9	459.7	0.003 8	1.003 1	no change	down	no change	no change
trans-Ferulic acid	193.050 8	296.6	0.000 1	1.614 6	down	down	down	down
Galactaric acid	209.030 2	77.5	0.001 7	1.450 4	up	no change	no change	no change
Milrinone	210.067 1	609.4	0.004 5	1.762 7	no change	no change	no change	no change
Tridecanoic acid	214.108 6	393.8	0.050 0	2.001 8	no change	no change	no change	down
N-Acetyl-D-glucosamine	221.154 8	855.3	0.010 5	1.773 0	no change	no change	no change	no change
Aciclovir	225.080 3	425.4	0.006 0	1.062 3	down	no change	down	down
Xylitol 5-phosphate	231.027 7	100.4	0.024 8	1.257 3	up	no change	up	no change
Equol	241.087 2	685.9	0.003 2	1.631 0	no change	down	no change	no change
Uridine	243.061 8	166.7	0.019 9	2.366 6	down	down	no change	no change
Pyridoxal phosphate	247.028 0	317.9	0.011 7	1.148 0	up	no change	no change	no change
Shikimate 3-phosphate	253.017 8	470.8	0.003 9	2.324 5	no change	no change	no change	down
Palmitic acid	255.233 1	874.8	0.002 3	1.503 0	up	no change	no change	no change
Zidovudine	267.090 7	459.3	0.000 0	1.243 5	up	up	up	up
Norizalpinin	269.045 6	471.3	0.013 3	1.542 7	no change	no change	down	no change
3＇-Hydroxydaidzein	269.045 5	537.3	0.011 1	1.040 4	no change	no change	no change	no change
Arbutin	272.095 7	569.0	0.004 3	2.042 9	down	no change	no change	down
beta-D-3-Ribofuranosyluric acid	281.053 9	128.2	0.021 9	1.251 5	no change	no change	no change	no change
Dihydrotestosterone	289.165 9	322.0	0.000 0	1.042 4	up	no change	up	up
Kaempferide	299.056 3	687.9	0.000 1	1.744 2	up	n o change	no change	no change
Morin	301.037 7	369.6	0.036 2	1.052 9	down	no change	no change	no change
（S，E）-Zearalenone	317.139 2	787.7	0.001 7	2.381 2	no change	no change	no change	no change
GMP	344.039 7	149.6	0.001 8	1.044 0	no change	up	no change	down
Pirenzepine	350.163 4	521.1	0.000 0	1.605 7	up	no change	up	down
Sinigrin	359.033 7	419.2	0.000 0	2.481 8	no change	up	no change	up
Deoxycholic acid	392.288 1	790.8	0.019 7	1.005 2	no change	no change	no change	no change
Carvedilol	405.189 0	563.4	0.021 2	1.369 0	down	down	no change	no change
Allocholic acid	407.281 7	677.7	0.031 1	1.169 0	down	down	down	no change
Daidzin	415.101 5	491.3	0.040 8	1.823 3	no change	no change	no change	no change
Astragalin	448.108 5	464.7	0.028 8	2.674 4	no ch ange	no change	no change	no change

基于代谢组学探讨三七对肾纤维化大鼠线粒体能量代谢的影响

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黄志敏 ¹ , 陆良喜 ² , 吴金玉 ¹

中华中医药学刊 | 国家项目点击 2025,43(12): 47-54

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中华中医药学刊 | 国家项目点击 2025, 43(12): 47-54

基于代谢组学探讨三七对肾纤维化大鼠线粒体能量代谢的影响

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黄志敏¹, 陆良喜², 吴金玉¹

作者信息

^1.广西中医药大学第一附属医院，广西中医药防治医学分子生物重点实验室，广西南宁 530023

^2.广西中医药大学第一附属医院仁爱分院，广西南宁 530001

黄志敏（1988-），女，广西贵港人，主治医师，博士，研究方向：中医药防治风湿免疫疾病。

通讯作者:

吴金玉（1965-），女，广东广州人，教授、主任医师，博士研究生导师，博士，研究方向：中医药防治风湿免疫疾病。E-mail：wujinyu0109@sina.com。

Investigating Effect of Sanqi（Notoginseng Radix et Rhizoma）on Mitochondrial Energy Metabolism in Rats with Renal Fibrosis Based on Metabolomics

Zhimin HUANG¹, Liangxi LU², Jinyu WU¹

Affiliations

^1.The First Affiliated Hospital of Guangxi University of Chinese Medicine，Guangxi Key Laboratory of Molecular Biology of Preventive Medicine of Traditional Chinese Medicine，Nanning 530023，Guangxi，China

^2.Ren'ai Branch of The First Affiliated Hospital of Guangxi University of Chinese Medicine，Nanning 530001，Guangxi，China

出版时间: 2025-12-10 doi: 10.13193/j.issn.1673-7717.2025.12.008

文章导航

摘要

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目的

研究三七对血瘀证阿霉素肾纤维化大鼠线粒体能量代谢的影响。

方法

将30只SD大鼠随机分为6组：正常组、模型组、三七低剂量组、三七中剂量组、三七高剂量组、阳性对照组，每组5只。采用电镜观察大鼠肾组织线粒体结构，化学法检测肾组织三磷酸腺苷（Adenosine triphosphate，ATP）、二磷酸腺苷（Adenosine diphosphate，ADP）、一磷酸腺苷（Adenosinemonophosphate，AMP）含量、Na⁺-K⁺-ATP酶、Ca²⁺-Mg²⁺-ATP酶活性、线粒体呼吸链复合体酶Ⅰ～Ⅳ活性。采用液相色谱仪、质谱仪对尿液进行代谢物成分分析，获得代谢差异物后，进行KEGG代谢通路富集。

结果

电镜下可见模型组大鼠肾组织线粒体结构不完整，三七可以维持肾组织线粒体结构稳态。三七可以提高肾组织线粒体ATP含量、Na⁺-K⁺-ATP酶、Ca²⁺-Mg²⁺-ATP酶、线粒体呼吸链复合体酶Ⅰ、Ⅱ、Ⅲ、Ⅳ活性；降低肾组织线粒体ADP、AMP含量。进行三七低、中、高剂量组、模型组和正常组分析对比，筛查出11个差异尿液代谢产物，分别为Ferulic acid、Morin、Arabitol、Acetamide、Biotin、Allantoic acid、6-Methylmercaptopurine、4-Hydroxy-2-quinolone、Aminopentanedioate、6-Methyladenine、Moupinamide。进一步对各实验组动物尿液代谢物KEGG通路富集分析结果显示：醛固酮调控的钠重吸收通路差异具有显著统计学意义。

结论

三七通过调节差异尿液代谢产物的代谢，调控醛固酮调节Na⁺重吸收通路，从多靶点、多途径改善血瘀证慢性肾脏疾病（Chronic Kidney Diseases，CKD）大鼠的线粒体能量代谢，发挥抗肾纤维化作用。

关键词

慢性肾脏病 / 三七 / 肾纤维化 / 线粒体能量代谢 / 代谢组学

Abstract

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Objective

To study the effectof Sanqi（Notoginseng Radix et Rhizoma）onmitochondrial energy metabolism of rats with adriamycin induced kidney fibrosis with blood stasis.

Methods

Thirty rats were divided into 6 groups random ly，including normal group，model group，Sanqi（Notoginseng Radix et Rhizoma）low-dose group，Sanqi（Notoginseng Radix et Rhizoma）medium-dose group，Sanqi（Notoginseng Radix et Rhizoma）high-dose group and positive control group，with 5 rats in each group.Themitochondrial structure of rat renal tissue was observed by electron microscopy.The contents of adenosine triphosphate（ATP），adenosine diphosphate（ADP），adenosine monophosphate（AMP），the activities of Na⁺ -K⁺ -ATPase，Ca²⁺ -Mg²⁺-ATPase and the activities ofmitochondrial respiratory chain complex enzymeⅠ-Ⅳwere detected by chemical method.The metabolites of urine were analyzed by liquid chromatograph and mass spectrometer.The differential metabolites were enriched by Kyoto Encyclopedia of Genes and Genomes（KEGG）metabolic pathway.

Results

Under electron microscope，the mitochondrial structure of renal tissue in the model group was incomplete，and Sanqi（Notoginseng Radix et Rhizoma）could maintain the homeostasis of renalmitochondrial structure.Sanqi（Notoginseng Radix et Rhizoma）could increase the mitochondrial ATP contentof the renal tissue，the activities of Na⁺-K⁺-ATPase，Ca²⁺-Mg²⁺-ATPase andmitochondrial respiratory chain complex enzymeⅠ-Ⅳ.Sanqi（Notoginseng Radix et Rhizoma）could reduce the contents of mitochondrial ADP and AMP of renal tissue.After analysis and comparison among the groups，11 different urine metabolites were screened，including ferulic acid，forin，arabitol，acetamide，biotin，allantoic acid，6-methylmercaptopurine，4-hydroxy-2-quinolone，aminopentanedioate，6-methyladenine and moupinamide.Further enrichment of urinemetabolites by KEGG in different experimental groups showed that the aldosterone-regulated sodium reabsorption signal pathway was significantly different.

Conclusion

Sanqi（Notoginseng Radix et Rhizoma）regulates the differential urine metabolites and raldosterone-regulated sodium reabsorption signal pathway.Sanqi（Notoginseng Radix et Rhizoma）can improve mitochondrial energy metabolism and renal fibrosis in chronic kidney diseases（CKD）rats with blood stasis bymulti-target and multi-pathway.

Key words

chronic kidney disease / Sanqi（Notoginseng Radix et Rhizoma） / renal fibrosis / mitochondrial energy metabolism / metabolomics

引用本文

黄志敏, 陆良喜, 吴金玉. 基于代谢组学探讨三七对肾纤维化大鼠线粒体能量代谢的影响. 中华中医药学刊, 2025 , 43 (12) : 47 -54 . DOI: 10.13193/j.issn.1673-7717.2025.12.008

Zhimin HUANG, Liangxi LU, Jinyu WU. Investigating Effect of Sanqi（Notoginseng Radix et Rhizoma）on Mitochondrial Energy Metabolism in Rats with Renal Fibrosis Based on Metabolomics[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (12) : 47 -54 . DOI: 10.13193/j.issn.1673-7717.2025.12.008

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慢性肾脏疾病（Chronic Kidney Diseases，CKD）被广泛认为是一个主要的公共卫生问题，影响着全球10%的人口健康，并且每年的患病率持续增加，数百万人因缺乏有效地治疗而死亡^[1]，到2040年预计CKD将成为全球第5大最常见的死亡疾病^[2]。线粒体是存在于真核细胞内的由双层膜包被的细胞器。肾脏近端肾小管细胞占肾脏皮质细胞的比例高达90%，近端肾小管细胞是体内第二高密度线粒体场所，其线粒体含量和耗氧量仅次于心脏，其产生大量ATP的同时也需要消耗大量能量维持正常功能^[3]。肾脏是能量代谢的重要场所。肾损伤早期已经导致线粒体活性氧（mitochondrial reactive oxygen species，mtROS）的过量产生，ATP产生的下降^[4]，促进炎症通路活化，炎性细胞因子和趋化因子释放增多，持续炎症启动肾纤维化进程。因此，线粒体功能障碍是肾纤维化发病过程中的关键环节。

目前“肾虚血瘀”是肾纤维化基本病因病机已成为医家共识，“瘀”贯穿肾纤维化病程始终。三七“活血化瘀、补虚强健”的功效与其病机高度契合。前期的研究表明，三七可以通过多途径减轻CKD微炎症状态、延缓肾纤维化进程的作用^[5-7]。本研究基于代谢组学探讨三七对肾纤维化大鼠线粒体能量代谢的影响，阐明三七改善CKD肾脏能量代谢的作用机制。

1　材料与方法

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1.1　实验动物

SPF级雄性SD大鼠30只，体质量（220±30）g。实验所需动物从湖南斯莱克景达实验动物有限公司购买，公司许可证号为SCXK（湘）2019-0004。动物实验伦理审查批号：DW20221221-241。在广西中医药防治医学分子生物重点实验室饲养。

1.2　主要的仪器、试剂及药物

全自动生化分析仪（罗氏公司，cobas702），光学显微镜（日本尼康，Nikon Eclipse E100），多功能酶标仪（Molecular Devices，Flexstation3），透射电子显微镜（HT7800/HT7700，HITACHI），液相色谱仪（Thermo，Vanquish），质谱仪（Thermo，Orbitrap Exploris 120），HE染液（上海源科，G2006），ATP含量测定试剂盒（南京建成生物工程研究所，A095-1-1），ADP含量测定试剂盒（Abcam，ab83359），AMP含量测定试剂盒（Abcam，ab273275），ATP酶测定试剂盒（南京建成生物工程研究所，A016-2），线粒体呼吸链复合体Ⅰ/NADH-CoQ还原酶活性检测试剂盒（北京索莱宝公司，BC0515）线粒体呼吸链复合体Ⅱ/琥珀酸-辅酶Q还原酶活性检测试剂盒（北京索莱宝公司，BC3235），线粒体呼吸链复合体Ⅲ/CoQ-细胞色素C还原酶活性检测试剂盒（北京索莱宝公司，BC3245），线粒体呼吸链复合体Ⅳ/细胞色素C氧化酶活性检测试剂盒（北京索莱宝公司，BC0945），BCA试剂盒（碧云天，P0012S）。三七：中药配方颗粒（江苏省江阴市天江药业有限公司）。盐酸贝那普利5 mg/片（北京诺华制药有限公司，国药准字H20000292）。

1.3　血瘀证阿霉素肾纤维化大鼠模型制备

参照前期研究中阿霉素肾纤维化大鼠模型的建立，镜检出现节段甚至球性肾小球硬化、球囊粘连、肾小管上皮细胞空泡变性、肾间质纤维化及炎症细胞浸润等病理改变则提示肾纤维化造模成功^[7]。在阿霉素肾纤维化大鼠模型的基础上建立血瘀证模型^[8]：在手术后6周，以0.1 mg/kg剂量盐酸肾上腺素注射液皮下注射于造模的大鼠，2 h后置于4℃冷水中游泳5 min，连续2周。以血液流变学改变评估血瘀证模型。

1.4　实验分组与给药方法

将30只清洁级SD雄性大鼠，数字表随机分为正常组、模型组、三七低剂量组、三七中剂量组、三七高剂量组、阳性对照组（贝那普利组），每组5只。正常组大鼠正常条件饲养，不造模；其余组大鼠按上法造模。造模完成后，阳性对照组大鼠每天给予贝那普利片给药，参考陈奇主编《中药药理实验方法学》体表面积等效剂量换算比率按人常用量5 mg/d，大鼠剂量5 mg×0.018＝0.09 mg，200 g体质量大鼠的剂量为0.09 mg，0.09 mg/0.2 kg＝0.45 mg/kg，溶于0.9%氯化钠溶液，按体质量灌胃给药。中药组按人和动物体表面积换算公式：大鼠中药给药剂量依据人-大鼠体表面积换算（1∶6.25），并按临床成人用药量的1、2、4倍剂量给药，三七低、中、高剂量组分别予以含生药0.45、0.9、1.8 g/kg三七颗粒水冲剂。正常组和模型组大鼠每天给予等体积的0.9%氯化钠溶液。各组皆按1 mL/100 g体质量灌胃，1次/d，连续8周。给药完成后腹主动脉采血后摘除左肾，放入液氮或固定液中保存。

1.5　指标检测

1.5.1　肾组织线粒体结构

肾组织经过固定液固定、脱水、包埋、染色，透射电镜观察肾组织线粒体结构。

1.5.2　肾组织线粒体能量代谢相关指标

严格按照ATP含量测定试剂盒、ADP含量测定试剂盒、AMP含量测定试剂盒、ATP酶测定试剂盒、线粒体呼吸链复合体Ⅰ/NADH-CoQ还原酶活性检测试剂盒、线粒体呼吸链复合体Ⅱ/琥珀酸-辅酶Q还原酶活性检测试剂盒、线粒体呼吸链复合体Ⅲ/CoQ-细胞色素C还原酶活性检测试剂盒、线粒体呼吸链复合体Ⅳ/细胞色素C氧化酶活性检测试剂盒操作分别检测ATP、ADP、AMP含量，Na⁺-K⁺-ATP酶、Ca²⁺-Mg²⁺-ATP酶活性、线粒体呼吸链复合体酶Ⅰ-Ⅳ活性。

1.5.3　尿液代谢组学分析

（1）色谱条件：Thermo Vanquish（Thermo Fisher Scientific，USA）超高效液相系统，使用ACQUITY UPLC® HSST3（2.1×150 mm，1.8μm）（Waters，Milford，MA，USA）色谱柱，0.25 mL/min的流速，40℃的柱温，进样量2 μL。正离子模式，流动相为0.1%甲酸乙腈（C）和0.1%甲酸水（D），梯度洗脱程序为0～1 min，2% C；1～9 min，2%～50%C；9～12 min，50% ～98% C；12～13.5 min，98% C；13.5～14 min，98%～2% C；14～20 min，2% C。负离子模式，流动相为乙腈（A）和5 mmol/L甲酸铵水（B），梯度洗脱程序为0～1 min，2% A；1～9 min，2%～50% A；9～12 min，50%～98% A；12～13.5 min，98% A；13.5～14 min，98% ～2% A；14～17 min，2% A。

（2）质谱条件：Thermo Orbitrap Exploris 120质谱检测器（Thermo Fisher Scientific，USA），电喷雾离子源（ESI），正负离子模式分别采集数据。正离子喷雾电压为3.50 kV，负离子喷雾电压为-2.50 kV，鞘气30 arb，辅助气10 arb。毛细管温度325℃，以分辨率60 000进行一级全扫描，一级离子扫描范围100～1000 m/z，并采用HCD进行二级裂解，碰撞电压为30%，二级分辨率为15 000，采集信号前4离子进行碎裂，同时采用动态排除去除无必要的MS/MS信息。

（3）数据处理与分析：通过 Proteowizard 软件包（v3.0.8789）中MSConvert工具将原始质谱下机文件转换为mzXML文件格式。采用RXCMS软件包进行峰检测、峰过滤、峰对齐处理，得到物质定量列表，参数设置有bw＝2，ppm＝15，peakwidth＝c（5，30），mzwid＝0.015，mzdiff＝0.01，method＝“centWave”。采用公共数据库HMDB、massbank、LipidMaps、mzcloud、KEGG及自建物质库进行物质的鉴定，参数设置为<30 ppm。使用总峰归一化，即基于样本中单一代谢物定量值与所有代谢物的定量值总和的比例换算，实现归一化，进行数据校正，消除系统误差。

采用R软件包Ropls分别对样本数据进行主成分分析（PCA）、偏最小二乘判别分析（PLS-DA），并分别绘制得分图，展示各样本间代谢物组成的差异。用置换检验方法对模型进行过拟合检验。

R2X和R2Y分别表示所建模型对X和Y矩阵的解释率，Q2表示模型的预测能力，它们的值越接近于1表明模型的拟合度越好，训练集的样本越能够被准确划分到其原始归属中。根据统计检验计算P value值、OPLS-DA降维方法计算变量投影重要度（VIP）、fold change计算组件差异倍数，衡量各代谢物组分含量对样本分类判别的影响强度和解释能力，辅助标志代谢物的筛选。当P value值<0.05和VIP值>1时，认为代谢物分子具有统计学意义。

（4）通路分析：采用MetaboAnalyst软件包对筛选差异代谢分子进行功能通路富集和拓扑学分析。富集得到的通路采用KEGG Mapper可视化工具进行差异代谢物与通路图的浏览。

1.6　统计分析

采用SPSS 22.0软件进行统计分析，计量资料符合正态分布且方差齐以均数±标准差表示，不符合正态分布或方差不齐以中位数（四分位间距）表示。符合正态分布方差齐的多样本比较采用单因素方差分析，组间两两比较采用LSD-t检验；不符合正态分布或方差不齐时采用秩和检验（Kruskalwallis），两两比较采用Wilcoxon法。P<0.05为差异有统计学意义。

2　结果

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2.1　各组大鼠肾组织线粒体结构的变化

大鼠肾组织透射电镜显示，正常组大鼠肾组织线粒体形态清晰，嵴膜系统完整，微绒毛形态清晰完整，自噬处于相对较低的水平；模型组细胞中出现大量空泡，线粒体数量减少，肿胀，嵴消失，微绒毛脱落，管腔内见大量细胞碎片，自噬小体数量明显增加；三七中、高剂量组及阳性对照组大部分细胞线粒体形态规整、完好，管腔内见少量细胞碎片，自噬体数量较少与正常对照组相比差异不明显；三七低剂量组与模型组相似，但是病变程度稍轻。见插页Ⅹ图1。

2.2　各组大鼠线粒体能量代谢的变化

2.2.1　大鼠肾组织ATP、ADP以及AMP含量比较分析

与正常组比较，模型组，三七低、中、高剂量组和阳性对照组肾组织线粒体ATP含量显著降低（P<0.05）；与模型组比较，三七中、高剂量组和阳性对照组肾组织线粒体ATP含量显著升高（P<0.05）。与正常组比较，模型组、三七低、中、高剂量组和阳性对照组肾组织线粒体ADP含量显著升高（P<0.05）；与模型组比较，三七低、中、高剂量组和阳性对照组肾组织线粒体ADP含量显著降低（P<0.01）。与正常组比较，模型组、三七低、中剂量组和阳性对照组肾组织线粒体AMP含量显著升高（P<0.05），三七高剂量组AMP有升高趋势，差异无统计学意义；与模型组比较，三七低、中、高剂量组和阳性对照组肾组织线粒体AMP含量显著降低（P<0.05）。见表1。

2.2.2　大鼠肾组织ATP酶活性比较分析

与正常组比较，模型组、三七低、中、高剂量组和阳性对照组肾组织Na⁺-K⁺-ATP、Ca²⁺-Mg²⁺-ATP酶活性明显降低；与模型组比较，三七低、中、高剂量组和阳性对照组肾组织中Na⁺ -K⁺ -ATP、Ca²⁺-Mg²⁺-ATP酶活性明显升高。见表2。

2.2.3　肾组织线粒体呼吸链复合体活性比较分析

与正常组比较，模型组、三七低、中、高剂量组和阳性对照组肾组织线粒体呼吸链复合体酶Ⅰ、Ⅳ活性显著降低；与模型组比较，三七中、高剂量组和阳性对照组肾组织线粒体呼吸链复合体酶Ⅰ、Ⅳ活性显著升高。与正常组比较，模型组、三七低、中剂量组肾组织线粒体呼吸链复合体酶Ⅱ活性显著降低；与模型组比较，三七低、中、高剂量组和阳性对照组肾组织线粒体呼吸链复合体酶Ⅱ活性显著升高。与正常组比较，模型组、三七低、中、高剂量组和阳性对照组肾组织线粒体呼吸链复合体酶Ⅲ活性显著降低；与模型组比较，三七低、中、高剂量组和阳性对照组肾组织线粒体呼吸链复合体酶Ⅲ活性显著升高。见表3。

2.3　尿液代谢组学结果分析

2.3.1　大鼠尿液代谢质谱分析

正、负离子模式下各组大鼠尿液色谱图（插页Ⅺ图2、插页Ⅺ图3），不同颜色代表不同组别。趋势越相似，说明重复性良好，结果可靠。

2.3.2　主成分分析（PCA）

PCA作为一种无监督模式识别方式，能够反映数据的原始状态，在整个实验过程中，仪器具有良好的稳定性，样品处于受控状态，实验结果可靠。如插页Ⅺ图4所示，不同组别尿液样本在图中呈现出分离状态。正常组（N-Con）与模型组（Model）明显分离。

2.3.3　偏最小二乘法判别分析（PLS-DA）

为了探究在大鼠尿液中显著改变的与肾纤维化相关的代谢产物，进一步通过PLS-DA方法对各组数据进行分析。如插页Ⅻ图5所示，正常组、模型组、阳性对照组、三七低、中、高剂量组在所建立的数据模型中表现出良好的拟合度和预测能力（正离子：R² X：0.357，R² Y：0.997，Q²：0.914；负离子：R² X：0.345，R² Y：0.997，Q²：0.882）。

2.3.4　差异代谢物的分析

（1）差异代谢物火山图：如插页插页ⅩⅢ图6所示，模型组与正常组总差异代谢物数为255，其中上调差异代谢物数为114，下调差异代谢物数为141；模型组与三七低剂量组总差异代谢物数为204，其中上调差异代谢物数为104，下调差异代谢物数为100；模型组与三七中剂量组总差异代谢物数为162，其中上调差异代谢物数为56，下调差异代谢物数为106；模型组与三七高剂量组总差异代谢物数为202，其中上调差异代谢物数为99，下调差异代谢物数为103；模型组与阳性对照组总差异代谢物数为181，其中上调差异代谢物数为61，下调差异代谢物数为120。

（2）差异代谢物筛选结果：基于VIP值、t检验的P值和离子在组间的变化倍数（foldchange，FC）筛选差异物质。当P value值<0.05和VIP值>1时，认为代谢物分子具有统计学意义。各实验组相比有154个差异基因，其中与正常组相比，模型组共有25个代谢物显著下调、48个代谢物显著上调（表4）；三七各剂量组与模型组相比，筛选出主要的代谢物11个，包括D-Arabitol、1H-Indole-3-acetamide、Biotin、Moupinamide、Allantoic acid、trans-Ferulic acid、6-Methylmercaptopurine、6-Methyladenine、4-Hydroxy-2-quinolone、3-Aminopentanedioate和Morin（插页Ⅻ图7、插页ⅩⅣ图8-图9、插页ⅩⅤ图10-图11、插页ⅩⅥ图12-图13、插页ⅩⅦ图14-图15、插页ⅩⅧ图16-图17）。

2.3.5　差异代谢物通路分析

基于KEGG代谢通路，采用MetPA数据库分析各组差异代谢物相关代谢通路。结果如表4和插页ⅩⅨ图18所示，潜在代谢标记物主要参与78条代谢通路，其中醛固酮调控的钠重吸收（Aldosterone-regulated sodium reabsorption）代谢通路P值小于0.05，Imapact值分为0.3，说明本次检测到的差异代谢物对该通路的影响显著。

3　讨论

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线粒体是体内ATP合成的主要场所，ATP生成与呼吸作用的耦合被称为氧化磷酸化，氧化磷酸化是细胞代谢的中心，是真核生物能量生产的关键，被称为“细胞动力工厂”。线粒体氧化磷酸化依赖于线粒体呼吸链，它由4种主要的酶复合物和2个移动电子载体组成。同时，三羧酸循环、钙信号通路的稳态、细胞凋亡、活性氧（reactive oxygen species，ROS）生成、脂肪酸氧化代谢等线粒体功能由构成氧化磷酸化酶复合体维持。细胞内ATP参与能量转移，而在细胞外环境中ATP作为损伤相关分子模式（damage-associated molecular pattern，DAMP）并刺激炎症反应，尽管ATP的释放会促进损伤，但这一过程对于促进组织修复也是必不可少^[9]。在早期CKD阶段已存在线粒体功能异常，ATP释放增加。有研究结果表明，在5/6肾切除CKD模型中，模型组观察到自第2天以来复合体Ⅰ活性永久性降低，术后第7、14和28天复合体Ⅲ活性下降，早期肾组织线粒体β-氧化降低，提示线粒体生物功能损伤是肾损伤的早期事件，线粒体损伤时间上的持续性加重了CKD的发展^[10]。肾损伤早期mtROS的过量产生，特别是由于线粒体DNA拷贝数的减少，导致线粒体膜电位的丧失和ATP产生的下降^[4]。糖尿病小鼠肾脏线粒体DNA拷贝数持续下降，伴有ATP产生下调^[11]。转化生长因子-β1（Transforming growth factor-β1，TGF-β1）处理的肾巨噬细胞线粒体表现出超氧化物水平增加，ATP生成减少，巨噬细胞通过调节磷酸酶和紧张素同源诱导激酶（phosphatase and tensin homolog-induced kinase1，PINK1）/线粒体融合蛋白（mitofusin-2，MFN2）/E3泛素连接酶（E3 ubiquitin ligase encoded by Prkn，parkin）介导的线粒体自噬通路对肾纤维化起保护作用^[12]。我们的研究结果表明在血瘀证阿霉素肾纤维化大鼠肾组织中ATP水平显著下降，这与WANG等^[13]研究发现CKD组线粒体ATP水平和基底线粒体耗氧率显著降低的结果一致。我们的研究发现，ATP水平下降可能与线粒体生物功能损伤，呼吸链复合体Ⅰ、复合体Ⅱ、复合体Ⅲ、复合体Ⅳ活性下降，ATP酶活性降低密切相关。

代谢组学是继基因组学、蛋白质组学后的一门新兴学科，是一门系统研究生物体某一部位细胞、血液、体液小分子代谢产物的科学，其主要科研方法是收集和筛选出代谢产物，然后比较不同代谢物之间的差异，反映机体不同生理、病理状态下或内外因素影响下代谢物的代谢轮廓变化，得出代谢物的变化趋势和规律，以进一步揭示某种病理现象和疾病发病机制或者药物的作用机制^[14]。肾脏是机体重要的代谢场所，各类代谢终产物的改变反映肾脏疾病的发生发展，代谢组学为肾脏疾病的研究提供了新的思路和方向，相关研究日益增多，由此发现的代谢物有些已被证实可以作为肾脏疾病诊断及预后的生物学标志物应用于临床，如肾损伤分子-1（kidney injurymolecule 1，KIM-1）^[15]、中性粒细胞明胶酶相关脂质运载蛋白（neutrophil gelatinase-associated lipocalin，NGAL）^[16]等。本研究进行了三七低、中、高剂量组及模型组和正常组尿液代谢物分析对比，筛查出11个差异尿液代谢产物。目前的研究表明其中一些代谢差异物参与CKD发生发展进程。Ferulic acid可以减轻糖尿病肾病（diabetic nephropathy，DN）大鼠肾损伤，可能机制是通过调节丝裂原激活的蛋白激酶/MAP激酶（mitogen-activated protein kinase，MAPK）、核因子-κB（nuclear factor kappa，NF-κB）通路、内源性和外源性凋亡通路，减轻炎症反应、自噬损伤和肾小管细胞凋亡^[17]。临床运用中发现Ferulic acid联合厄贝沙坦可以明显减轻慢性肾衰竭（chronic renal failure，CRF）患者体内血清炎性因子，改善肾功能^[18]。Morin通过抗炎、抗凋亡、抗氧化和激活自噬保护顺铂诱导的肾损伤^[19]。腺嘌呤诱导的CKD小鼠模型中，Morin通过减少基质金属蛋白酶-2（matrixmetalloproteinase-2，MMP-2）、MMP-9蛋白的表达，降低单核细胞趋化蛋白-1（monocyte chemoattractant protein-1，MCP-1）和环氧合酶-2（cyclooxygenase-2，COX-2）表达，从而降低炎症水平，改善肾功能^[20]。儿童CKD 1～2期尿液中Arabitol含量比CKD 3～5期显著升高，这与本研究正常组尿液代谢物中Arabitol含量比模型组显著升高的研究结果类似^[21]。一项研究发现DN患者与正常人相比较，其血清代谢物中6-Methylmercaptopurine差异显著，可作为DN早期识别的潜在生物标志物^[22]。

本研究进一步对CKD大鼠各实验组尿液代谢物KEGG通路富集分析结果显示醛固酮调控的钠重吸收通路差异显著。这与SZMIT S等^[23]的研究结果相似，他运用转录组学对急性心力衰竭肌酐正常与升高的患者外周血基因筛查并进行通路分析，显示调控最显著的信号通路是醛固酮调控的钠重吸收，进一步研究发现患者Na⁺/K⁺-ATP酶的表达差异明显。醛固酮是CKD肾纤维化病理过程的关键因子，作用于肾血管、肾细胞（肾小球系膜细胞、足细胞、血管平滑肌细胞、小管上皮细胞、间质成纤维细胞）和浸润性炎症细胞，诱导ROS产生，上调上皮生长因子受体（epithelial growth factor receptor，EGFR）、1型血管紧张素（angiotensin type 1，AT1）受体的表达，激活NFκB、激活蛋白1（activin 1，AP-1）、TGF-β等的表达，最终导致肾脏纤维化^[24]。醛固酮诱导的肾损伤以肾小管为主，尤其以远端肾小管明显^[25]。小鼠注射醛固酮后足细胞和肾小球中线粒体膜电位、ATP水平和线粒体DNA拷贝数下降^[26]。Na⁺在细胞生理功能中发挥重要作用，除了维持细胞外液和渗透压、影响细胞内外体液分布、参与维持酸碱平衡、维持细胞内外Na⁺-K⁺以及ATP的利用和生成等，2020年HERNANSANZAGUSTÍN P等^[27]研究发现线粒体Na⁺/Ca²⁺通道激活促进Na⁺进入基质，随后Na⁺与磷脂相互作用，降低线粒体内膜流动性和游离泛醌在复合物Ⅱ和复合物Ⅲ之间的迁移率，在复合物Ⅲ中产生超氧化物，这表明Na⁺通过与磷脂相互作用来控制线粒体氧化磷酸化系统功能，影响ATP的合成过程。因此，醛固酮诱导的能量代谢障碍是CKD肾纤维化的重要因素，醛固酮调控的钠重吸收通路是CKD肾纤维化能量代谢的主要调控途径。

本研究结果提示三七可以提高血瘀证CKD大鼠肾组织ATP含量及Na⁺-K⁺-ATP酶、Ca²⁺-Mg²⁺-ATP酶，线粒体呼吸链复合体酶Ⅰ、Ⅱ、Ⅲ、Ⅳ活性。三七通过调节差异尿液代谢产物Ferulic acid、Morin、Arabitol、Acetamide、Biotin、Allantoic acid、6-Methylmercaptopurine、4-Hydroxy-2-quinolone、Aminopentanedioate、6-Methyladenine和Moupinamide的代谢，调控醛固酮调节Na⁺重吸收通路，从多靶点、多途径改善血瘀证CKD大鼠的线粒体能量代谢，发挥抗肾纤维化作用。

基金

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国家自然科学基金地区科学基金项目(81960866)
国家中医药管理局高水平中医药重点学科建设项目-中医内科学(zyyzdxk-2023166)
中医学广西一流学科项目(桂教科研〔2022〕1号)

参考文献

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文献

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参考文献引证文献

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黄志敏，黄仁发，唐宇，等. 基于肠肾轴理论探讨三七注射液对慢性肾脏病大鼠肠黏膜功能和肠道菌群的影响［J］. 中华中医药学刊，2021，39（9）：156-159.

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2025年第43卷第12期

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doi: 10.13193/j.issn.1673-7717.2025.12.008

首发时间：2026-04-29
出版时间：2025-12-10

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出版历史

基金

国家自然科学基金地区科学基金项目(81960866)

国家中医药管理局高水平中医药重点学科建设项目-中医内科学(zyyzdxk-2023166)

中医学广西一流学科项目(桂教科研〔2022〕1号)

作者信息

^1.广西中医药大学第一附属医院，广西中医药防治医学分子生物重点实验室，广西南宁 530023

^2.广西中医药大学第一附属医院仁爱分院，广西南宁 530001

通讯作者:

吴金玉（1965-），女，广东广州人，教授、主任医师，博士研究生导师，博士，研究方向：中医药防治风湿免疫疾病。E-mail：wujinyu0109@sina.com。

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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组别	n	ATP	ADP	AMP
正常组	5	2.136±0.114	2.529±0.125	4.298（0.218）
模型组	5	0.878±0.145^a	6.033±0.344^a	11.430（1.634）^a
三七低剂量组	5	1.015±0.095^a	4.835±0.296^ab	9.272（0.735）^ab
三七中剂量组	5	1.279±0.117^ab	4.435±0.272^ab	8.287（0.120）^ab
三七高剂量组	5	1.882±0.154^ab	2.889±0.253^ab	4.707（0.347）^b
阳性对照组	5	1.896±0.176^ab	3.411±0.243^ab	5.834（0.411）^ab
F值/H值		74.017	125.381	27.126
P值		0.000	0.000	0.000

组别

ATP

ADP

AMP

正常组

2.136±0.114

2.529±0.125

4.298（0.218）

模型组

0.878±0.145^a

6.033±0.344^a

11.430（1.634）^a

三七低剂量组

1.015±0.095^a

4.835±0.296^ab

9.272（0.735）^ab

三七中剂量组

1.279±0.117^ab

4.435±0.272^ab

8.287（0.120）^ab

三七高剂量组

1.882±0.154^ab

2.889±0.253^ab

4.707（0.347）^b

阳性对照组

1.896±0.176^ab

3.411±0.243^ab

5.834（0.411）^ab

F值/H值

74.017

125.381

27.126

P值

0.000

组别	n	Na⁺-K⁺-ATP酶活性	Ca²⁺-Mg²⁺-ATP酶活性
正常组	5	5.838±0.281	3.314±0.092
模型组	5	2.561±0.133^a	1.261±0.106^a
三七低剂量组	5	3.132±0.175^ab	1.682±0.138^ab
三七中剂量组	5	3.722±0.188^ab	2.269±0.229^ab
三七高剂量组	5	4.771±0.275^ab	2.679±0.238^ab
阳性对照组	5	4.649±0.379^ab	2.762±0.240^ab
F值		113.655	82.937
P值		0.000	0.000

组别

Na⁺-K⁺-ATP酶活性

Ca²⁺-Mg²⁺-ATP酶活性

正常组

5.838±0.281

3.314±0.092

模型组

2.561±0.133^a

1.261±0.106^a

三七低剂量组

3.132±0.175^ab

1.682±0.138^ab

三七中剂量组

3.722±0.188^ab

2.269±0.229^ab

三七高剂量组

4.771±0.275^ab

2.679±0.238^ab

阳性对照组

4.649±0.379^ab

2.762±0.240^ab

F值

113.655

82.937

P值

0.000

组别	n	Ⅰ	Ⅱ	Ⅲ	Ⅳ
正常组	5	51.533±3.797	9.612（0.421）	12.720±1.003	13.157（1.878）
模型组	5	17.071±3.012^a	4.411（0.558）^a	3.902±0.233^a	5.205（1.234）^a
三七低剂量组	5	19.549±5.123^a	5.13（0.548）^ab	5.259±0.812^ab	5.239（1.582）^a
三七中剂量组	5	30.985±4.925^ab	5.47（0.459）^ab	7.311±1.015^ab	8.093（1.832）^ab
三七高剂量组	5	43.437±4.977^ab	7.896（3.096）^b	9.482±0.879^ab	10.702（1.811）^ab
阳性对照组	5	41.220±1.999^ab	7.425（3.649）^b	9.495±0.650^ab	9.640（0.287）^ab
F值/χ²值		55.647	22.492	78.314	26.079
P值		0.000	0.000	0.000	0.000

组别

Ⅰ

Ⅱ

Ⅲ

Ⅳ

正常组

51.533±3.797

9.612（0.421）

12.720±1.003

13.157（1.878）

模型组

17.071±3.012^a

4.411（0.558）^a

3.902±0.233^a

5.205（1.234）^a

三七低剂量组

19.549±5.123^a

5.13（0.548）^ab

5.259±0.812^ab

5.239（1.582）^a

三七中剂量组

30.985±4.925^ab

5.47（0.459）^ab

7.311±1.015^ab

8.093（1.832）^ab

三七高剂量组

43.437±4.977^ab

7.896（3.096）^b

9.482±0.879^ab

10.702（1.811）^ab

阳性对照组

41.220±1.999^ab

7.425（3.649）^b

9.495±0.650^ab

9.640（0.287）^ab

F值/χ²值

55.647

22.492

78.314

26.079

P值

0.000

名称	mz	rt	P .value	VIP	Model	LD	MD	HD
N-Methyl-2-pyrrolidinone	100.075 9	350.6	0.019 3	1.049 8	no change	no change	no change	no change
1-Aminocyclopropanecarboxylic acid	102.055 2	159.4	0.000 0	1.353 8	down	no change	up	no change
2-Phenylethanol	105.069 6	381.9	0.024 2	2.164 8	no change	no change	no change	up
Imidazole-4-acetaldehyde	111.055 1	121.1	0.012 0	2.388 3	up	no change	no change	up
Histamine	112.086 7	74.6	0.011 7	1.105 4	no change	no change	up	no change
Purine	120.044 2	694.3	0.006 1	2.348 1	up	up	no change	no change
Maltol	127.038 5	231.2	0.000 0	1.467 1	no change	up	no change	no change
（S）-2，3，4，5-tetrahydropyridine-2-carboxylate	128.070 3	341.5	0.000 7	1.234 4	no change	no change	no change	no change
5-Hydroxymethylfurfuryl alcohol	128.049 4	673.7	0.034 4	2.835 0	no change	down	down	down
Octanal	129.127 2	596.8	0.005 2	1.128 8	down	no change	no change	no change
5-Amino-2-oxopentanoic acid	131.070 0	199.0	0.027 2	2.152 7	no change	no change	no change	down
N-Acetyl-beta-alanine	132.065 0	162.3	0.047 5	1.792 8	up	up	no change	no change
1，3-Dihydro-（2H）-indol-2-one	134.059 9	452.4	0.002 3	1.407 2	no change	up	up	no change
Phosphonoacetate	140.070 4	299.7	0.034 9	2.038 5	up	no change	no change	up
Valpromide	144.137 9	474.4	0.018 8	2.297 4	no change	up	no change	no change
Acetylcholine	146.117 2	96.7	0.023 4	1.598 0	up	up	no change	up
O-Acetylserine	148.060 1	159.2	0.030 2	1.583 3	no change	down	no change	no change
Cuminaldehyde	149.095 8	488.1	0.012 0	1.704 1	down	down	no change	down
D-Arabitol	152.070 3	432.7	0.000 2	1.720 7	down	no change	down	down
Protocatechuic acid	155.106 4	537.4	0.013 6	1.700 3	no change	down	no change	no change
Tranexamic Acid	158.117 3	414.6	0.004 5	1.910 3	down	no change	down	down
D-Alanyl-D-alanine	160.096 6	442.1	0.008 5	1.166 0	up	no change	up	up
4-Hydroxy-2-quinolone	161.046 8	476.7	0.003 1	1.887 7	up	up	no change	no change
N-methyl-L-glutamic Acid	161.070 7	502.1	0.032 2	1.247 6	up	no change	no change	no change
Anabasine	163.038 7	591.9	0.004 1	1.874 3	no change	down	no change	no change
Isosafrole	163.075 2	868.4	0.003 4	1.661 0	up	up	up	up
Enol-phenylpyruvate	165.054 3	310.7	0.003 0	1.845 7	up	no change	up	up
4-Phenylbutyrate	165.090 6	545.7	0.001 8	1.166 5	no change	up	no change	no change
Epinephrine	166.086 2	377.7	0.000 2	1.499 5	no c hange	up	up	up
Desaminotyrosine	167.073 9	164.6	0.032 3	1.352 5	up	up	up	no change
Tropate	167.081 3	425.3	0.001 7	1.504 5	no change	up	up	no change
Perillic acid	167.106 1	617.9	0.002 2	1.505 2	no change	no change	down	no change
Quinolinic acid	167.012 6	74.7	0.003 0	1.479 4	no change	no change	no change	no change
Isopyridoxal	168.065 1	197.4	0.046 2	1.597 0	no change	no change	up	no change
Pyridoxamine	169.097 1	269.8	0.013 9	1.421 1	no change	no change	no change	no change
2-Biphenylol	171.076 4	298.5	0.001 3	1.137 9	down	no change	down	down
Iminoarginine	172.107 8	210.5	0.045 4	1.333 9	no change	no change	up	no change
Swainsonine	174.112 1	350.0	0.019 2	1.444 0	down	no change	no change	no change
Formiminoglutamic acid	175.071 0	101.7	0.023 0	1.512 9	no change	no change	no change	no change
1 H-Indole-3-acetamide	175.086 4	503.2	0.043 1	1.929 3	down	no change	no change	down
3-Methyl-L-tyrosine	178.086 1	325.5	0.006 0	2.552 8	no change	no change	no change	up
Methyleugenolu	179.106 4	792.0	0.002 0	1.352 7	up	no change	no change	up
5-Oxo-1，2-campholide	183.101 2	612.8	0.012 3	1.165 2	up	up	no change	no change
Sebacic acid	185.117 5	528.6	0.042 7	2.034 5	up	no change	no change	up
Deethylatrazine	188.070 3	673.5	0.022 0	2.026 3	up	up	up	up
Methyl（indol-3-yl）acetate	189.078 3	649.5	0.024 6	2.096 0	no change	no change	no change	up
Myristicin	193.085 4	515.9	0.002 3	2.131 1	up	no change	no change	up
Methoxamine	194.117 4	217.6	0.025 6	2.140 0	down	no change	no change	down
3，4-Methylenedioxyamphetamine	194.117 0	313.1	0.002 1	2.791 8	no change	no change	no change	down
（-）-Bornesitol	194.081 0	512.0	0.001 6	1.231 4	up	up	up	no change
Dopaquinone	196.059 9	375.3	0.043 0	1.788 0	no change	down	down	down
Dethiobiotin	197.127 9	209.0	0.000 3	1.345 3	up	up	up	up
N-Acetylhistidine	198.086 6	100.4	0.033 5	1.392 9	down	no change	no change	no change
Spermine	203.222 5	77.4	0.002 9	1.089 6	no change	no change	no change	no change
Bufotenin	205.137 2	177.1	0.015 4	1.260 8	no change	down	no change	no change
trans-Isoasarone	209.116 8	490.0	0.014 2	1.417 9	no change	up	no change	no change
Propoxur	210.112 3	467.3	0.005 9	2.200 1	up	up	up	up
（+）-7-Isojasmonic acid	211.132 4	481.2	0.000 1	1.072 9	up	up	up	up
3-Methyl-1-（2，4，6-trihydroxyphenyl）-1-butanone	211.096 0	515.9	0.031 2	2.018 0	no change	no change	no change	up
Apiole	223.095 4	570.2	0.005 7	1.875 3	up	up	up	no change
Terbutaline	226.143 1	651.6	0.007 8	2.487 9	no change	down	down	down
Pirbuterol	241.153 9	128.0	0.000 1	1.774 1	up	no change	up	no change
Ribavirin	244.078 6	96.9	0.003 4	1.272 0	up	no change	no change	down
Biotin	245.094 9	461.3	0.001 7	1.297 4	down	no change	no change	no change
Osthol	245.116 5	716.3	0.000 1	1.671 2	up	no change	up	no change
N-Acetyl-D-tryptophan	247.128 3	377.2	0.015 3	2.368 8	no change	no change	no change	up
D-Octopine	247.139 1	96.8	0.004 1	2.145 9	up	no change	no change	up
5-Hydroxyindoleacetylglycine	249.086 4	515.1	0.016 6	2.172 1	no change	no change	up	up
Citrinin	251.090 7	605.2	0.000 4	1.329 6	up	no change	up	up
16-Oxopalmitate	253.215 4	705.9	0.002 3	1.894 7	no change	down	no change	no change
16-Hydroxy hexadecanoic acid	255.230 8	844.2	0.036 8	1.898 8	no change	no change	no change	no change
Stearolic acid	263.236 2	868.1	0.000 8	2.952 8	down	down	down	down
gamma-Glutamyltyramine	266.120 7	454.9	0.000 0	1.732 3	up	up	up	up
Nevirapine	267.120 0	488.9	0.001 2	1.761 9	no change	up	up	up
Xanthoxic acid	267.162 8	667.4	0.043 1	1.620 8	no change	no change	no change	no change
Baicalein	271.179 7	702.9	0.000 0	1.909 4	no change	no change	up	no change
（5-L-Glutamyl）-L-glutamate	277.103 7	131.7	0.000 1	1.341 7	up	up	up	up
Sulfamethazine	279.092 6	749.0	0.040 8	1.030 1	no change	no change	no change	no change
Guanosine	284.098 4	280.3	0.034 0	1.141 6	no change	no change	no change	no change
9-OxoODE	295.225 6	867.6	0.008 8	2.429 9	up	up	no change	up
Enterolactone	299.126 8	594.6	0.002 1	1.547 7	up	no change	up	up
Dihydrocapsaicin	308.220 7	626.3	0.000 1	2.735 5	up	up	up	up
Moupinamide	314.123 7	174.4	0.019 1	1.143 0	down	no change	no change	no change
N-Acetylthienamycin	314.102 6	76.8	0.038 8	1.170 4	no change	no change	down	no change
Oxycodone	316.154 1	510.0	0.027 2	1.497 7	up	up	up	no change
Clostebol	323.182 7	653.5	0.004 4	1.738 5	no cha nge	no change	up	no change
Melibiose	325.112 6	322.2	0.015 2	2.389 3	no cha nge	no change	no change	no change
Bitertanol	338.194 7	732.1	0.001 0	2.094 7	no change	down	no change	no change
17alpha，21-Dihydroxypregnenolone	349.235 9	563.2	0.012 0	1.706 2	no change	no change	no change	no change
Cortisone	360.202 7	450.8	0.004 1	1.179 6	up	up	up	no change
Aldosterone	361.220 4	877.6	0.035 6	1.759 6	no change	no change	no change	no change
18-Hydroxycorticosterone	363.214 7	546.5	0.023 3	1.170 0	no change	no change	no change	down
Tangeritin	373.127 5	794.1	0.000 0	1.097 4	down	no change	down	down
S-Adenosylmethionine	398.239 8	792.9	0.016 6	1.347 2	no change	no change	no change	no change
N1，N8-Bis（4-coumaroyl）spermidine	438.240 2	489.8	0.003 8	1.191 6	down	no change	no change	down
Creatinine	112.984 7	921.7	0.011 9	2.422 1	no change	no change	no change	up
5-Aminopentanoic acid	115.920 9	813.7	0.017 1	1.614 0	no change	no change	down	down
Citramalic acid	129.018 8	142.0	0.001 0	1.893 8	down	no change	down	down
Glycyl-glycine	132.048 9	177.9	0.034 7	1.877 3	no change	no change	no change	down
Adenine	134.047 4	250.6	0.034 4	1.943 5	no change	no change	no change	no change
3-Dehydro-L-threonate	134.024 9	452.7	0.001 3	1.297 0	down	no change	down	down
Threonic acid	135.030 1	118.1	0.043 1	1.451 5	no change	no change	no change	no change
Dimethylbenzimidazole	145.040 8	431.2	0.005 8	2.076 3	no change	no change	no change	no change
D-Glutamine	145.062 2	88.5	0.017 8	1.212 3	no change	no change	no change	no change
3-Aminopentanedioate	146.046 0	94.3	0.000 9	1.252 4	up	no change	no change	no change
6-Methyladenine	148.063 0	350.2	0.009 5	1.673 5	up	no change	no change	up
D-Xylose	149.045 7	93.0	0.015 5	1.286 7	up	no change	no change	up
（R）-Mandelamide	151.060 6	983.4	0.011 8	1.356 9	no change	down	no change	no change
3-Hydroxyvalproic acid	159.102 6	331.4	0.030 8	1.513 1	no change	no change	no change	no change
Oxoadipic acid	160.040 6	454.3	0.022 4	2.288 4	no change	no change	no change	up
Umbelliferone	161.024 5	533.1	0.048 6	2.446 7	no change	no change	no change	no change
L-Phenylalanine	164.071 8	304.9	0.008 4	1.220 6	no change	no change	no change	up
6-Methylmercaptopurine	165.021 0	142.5	0.001 0	1.642 3	up	up	no change	no change
Terephthalate	165.019 7	388.4	0.022 1	1.642 2	no change	no change	no change	up
Hydantoin-5-propionic acid	171.041 4	95.7	0.018 2	1.498 5	up	no change	no change	no change
N-Acetylleucine	172.098 0	340.4	0.017 4	1.108 7	no change	no change	no change	up
Allantoic acid	175.048 3	82.7	0.000 1	1.035 9	down	no change	no change	no change
2-Dehydro-D-glucono-1，5-lactone	176.035 3	206.6	0.001 2	1.209 1	no change	down	no change	no change
D-Mannonate	177.040 5	81.4	0.002 7	1.195 3	no change	down	no change	no change
4-Hydroxyphenylpyruvic acid	179.035 2	303.3	0.000 4	1.048 9	no change	no change	no change	no change
D-Mannose	179.056 4	90.1	0.012 9	1.120 3	no change	no change	up	no change
Homovanillate	181.050 7	164.0	0.021 2	2.061 9	up	up	no change	no change
Hydroxyphenyllactic acid	181.050 5	253.8	0.000 0	2.968 4	no change	up	up	up
2＇，6＇-Dihydroxy-4＇-methoxyacetophenone	181.050 6	426.9	0.033 6	1.037 9	up	no change	up	no change
10-Oxodecanoate	186.121 9	459.7	0.003 8	1.003 1	no change	down	no change	no change
trans-Ferulic acid	193.050 8	296.6	0.000 1	1.614 6	down	down	down	down
Galactaric acid	209.030 2	77.5	0.001 7	1.450 4	up	no change	no change	no change
Milrinone	210.067 1	609.4	0.004 5	1.762 7	no change	no change	no change	no change
Tridecanoic acid	214.108 6	393.8	0.050 0	2.001 8	no change	no change	no change	down
N-Acetyl-D-glucosamine	221.154 8	855.3	0.010 5	1.773 0	no change	no change	no change	no change
Aciclovir	225.080 3	425.4	0.006 0	1.062 3	down	no change	down	down
Xylitol 5-phosphate	231.027 7	100.4	0.024 8	1.257 3	up	no change	up	no change
Equol	241.087 2	685.9	0.003 2	1.631 0	no change	down	no change	no change
Uridine	243.061 8	166.7	0.019 9	2.366 6	down	down	no change	no change
Pyridoxal phosphate	247.028 0	317.9	0.011 7	1.148 0	up	no change	no change	no change
Shikimate 3-phosphate	253.017 8	470.8	0.003 9	2.324 5	no change	no change	no change	down
Palmitic acid	255.233 1	874.8	0.002 3	1.503 0	up	no change	no change	no change
Zidovudine	267.090 7	459.3	0.000 0	1.243 5	up	up	up	up
Norizalpinin	269.045 6	471.3	0.013 3	1.542 7	no change	no change	down	no change
3＇-Hydroxydaidzein	269.045 5	537.3	0.011 1	1.040 4	no change	no change	no change	no change
Arbutin	272.095 7	569.0	0.004 3	2.042 9	down	no change	no change	down
beta-D-3-Ribofuranosyluric acid	281.053 9	128.2	0.021 9	1.251 5	no change	no change	no change	no change
Dihydrotestosterone	289.165 9	322.0	0.000 0	1.042 4	up	no change	up	up
Kaempferide	299.056 3	687.9	0.000 1	1.744 2	up	n o change	no change	no change
Morin	301.037 7	369.6	0.036 2	1.052 9	down	no change	no change	no change
（S，E）-Zearalenone	317.139 2	787.7	0.001 7	2.381 2	no change	no change	no change	no change
GMP	344.039 7	149.6	0.001 8	1.044 0	no change	up	no change	down
Pirenzepine	350.163 4	521.1	0.000 0	1.605 7	up	no change	up	down
Sinigrin	359.033 7	419.2	0.000 0	2.481 8	no change	up	no change	up
Deoxycholic acid	392.288 1	790.8	0.019 7	1.005 2	no change	no change	no change	no change
Carvedilol	405.189 0	563.4	0.021 2	1.369 0	down	down	no change	no change
Allocholic acid	407.281 7	677.7	0.031 1	1.169 0	down	down	down	no change
Daidzin	415.101 5	491.3	0.040 8	1.823 3	no change	no change	no change	no change
Astragalin	448.108 5	464.7	0.028 8	2.674 4	no ch ange	no change	no change	no change

名称

P .value

VIP

Model

N-Methyl-2-pyrrolidinone

100.075 9

350.6

0.019 3

1.049 8

no change

1-Aminocyclopropanecarboxylic acid

102.055 2

159.4

0.000 0

1.353 8

down

no change

2-Phenylethanol

105.069 6

381.9

0.024 2

2.164 8

no change

Imidazole-4-acetaldehyde

111.055 1

121.1

0.012 0

2.388 3

no change

Histamine

112.086 7

74.6

0.011 7

1.105 4

no change

Purine

120.044 2

694.3

0.006 1

2.348 1

no change

Maltol

127.038 5

231.2

0.000 0

1.467 1

no change

（S）-2，3，4，5-tetrahydropyridine-2-carboxylate

128.070 3

341.5

0.000 7

1.234 4

no change

5-Hydroxymethylfurfuryl alcohol

128.049 4

673.7

0.034 4

2.835 0

no change

down

Octanal

129.127 2

596.8

0.005 2

1.128 8

down

no change

5-Amino-2-oxopentanoic acid

131.070 0

199.0

0.027 2

2.152 7

no change

down

N-Acetyl-beta-alanine

132.065 0

162.3

0.047 5

1.792 8

no change

1，3-Dihydro-（2H）-indol-2-one

134.059 9

452.4

0.002 3

1.407 2

no change

Phosphonoacetate

140.070 4

299.7

0.034 9

2.038 5

no change

Valpromide

144.137 9

474.4

0.018 8

2.297 4

no change

Acetylcholine

146.117 2

96.7

0.023 4

1.598 0

no change

O-Acetylserine

148.060 1

159.2

0.030 2

1.583 3

no change

down

no change

Cuminaldehyde

149.095 8

488.1

0.012 0

1.704 1

down

no change

down

D-Arabitol

152.070 3

432.7

0.000 2

1.720 7

down

no change

down

Protocatechuic acid

155.106 4

537.4

0.013 6

1.700 3

no change

down

no change

Tranexamic Acid

158.117 3

414.6

0.004 5

1.910 3

down

no change

down

D-Alanyl-D-alanine

160.096 6

442.1

0.008 5

1.166 0

no change

4-Hydroxy-2-quinolone

161.046 8

476.7

0.003 1

1.887 7

no change

N-methyl-L-glutamic Acid

161.070 7

502.1

0.032 2

1.247 6

no change

Anabasine

163.038 7

591.9

0.004 1

1.874 3

no change

down

no change

Isosafrole

163.075 2

868.4

0.003 4

1.661 0

Enol-phenylpyruvate

165.054 3

310.7

0.003 0

1.845 7

no change

4-Phenylbutyrate

165.090 6

545.7

0.001 8

1.166 5

no change

Epinephrine

166.086 2

377.7

0.000 2

1.499 5

no c hange

Desaminotyrosine

167.073 9

164.6

0.032 3

1.352 5

no change

Tropate

167.081 3

425.3

0.001 7

1.504 5

no change

Perillic acid

167.106 1

617.9

0.002 2

1.505 2

no change

down

no change

Quinolinic acid

167.012 6

74.7

0.003 0

1.479 4

no change

Isopyridoxal

168.065 1

197.4

0.046 2

1.597 0

no change

Pyridoxamine

169.097 1

269.8

0.013 9

1.421 1

no change

2-Biphenylol

171.076 4

298.5

0.001 3

1.137 9

down

no change

down

Iminoarginine

172.107 8

210.5

0.045 4

1.333 9

no change

Swainsonine

174.112 1

350.0

0.019 2

1.444 0

down

no change

Formiminoglutamic acid

175.071 0

101.7

0.023 0

1.512 9

no change

1 H-Indole-3-acetamide

175.086 4

503.2

0.043 1

1.929 3

down

no change

down

3-Methyl-L-tyrosine

178.086 1

325.5

0.006 0

2.552 8

no change

Methyleugenolu

179.106 4

792.0

0.002 0

1.352 7

no change

5-Oxo-1，2-campholide

183.101 2

612.8

0.012 3

1.165 2

no change

Sebacic acid

185.117 5

528.6

0.042 7

2.034 5

no change

Deethylatrazine

188.070 3

673.5

0.022 0

2.026 3

Methyl（indol-3-yl）acetate

189.078 3

649.5

0.024 6

2.096 0

no change

Myristicin

193.085 4

515.9

0.002 3

2.131 1

no change

Methoxamine

194.117 4

217.6

0.025 6

2.140 0

down

no change

down

3，4-Methylenedioxyamphetamine

194.117 0

313.1

0.002 1

2.791 8

no change

down

（-）-Bornesitol

194.081 0

512.0

0.001 6

1.231 4

no change

Dopaquinone

196.059 9

375.3

0.043 0

1.788 0

no change

down

Dethiobiotin

197.127 9

209.0

0.000 3

1.345 3

N-Acetylhistidine

198.086 6

100.4

0.033 5

1.392 9

down

no change

Spermine

203.222 5

77.4

0.002 9

1.089 6

no change

Bufotenin

205.137 2

177.1

0.015 4

1.260 8

no change

down

no change

trans-Isoasarone

209.116 8

490.0

0.014 2

1.417 9

no change

Propoxur

210.112 3

467.3

0.005 9

2.200 1

（+）-7-Isojasmonic acid

211.132 4

481.2

0.000 1

1.072 9

3-Methyl-1-（2，4，6-trihydroxyphenyl）-1-butanone

211.096 0

515.9

0.031 2

2.018 0

no change

Apiole

223.095 4

570.2

0.005 7

1.875 3

no change

Terbutaline

226.143 1

651.6

0.007 8

2.487 9

no change

down

Pirbuterol

241.153 9

128.0

0.000 1

1.774 1

no change

Ribavirin

244.078 6

96.9

0.003 4

1.272 0

no change

down

Biotin

245.094 9

461.3

0.001 7

1.297 4

down

no change

Osthol

245.116 5

716.3

0.000 1

1.671 2

no change

N-Acetyl-D-tryptophan

247.128 3

377.2

0.015 3

2.368 8

no change

D-Octopine

247.139 1

96.8

0.004 1

2.145 9

no change

5-Hydroxyindoleacetylglycine

249.086 4

515.1

0.016 6

2.172 1

no change

Citrinin

251.090 7

605.2

0.000 4

1.329 6

no change

16-Oxopalmitate

253.215 4

705.9

0.002 3

1.894 7

no change

down

no change

16-Hydroxy hexadecanoic acid

255.230 8

844.2

0.036 8

1.898 8

no change

Stearolic acid

263.236 2

868.1

0.000 8

2.952 8

down

gamma-Glutamyltyramine

266.120 7

454.9

0.000 0

1.732 3

Nevirapine

267.120 0

488.9

0.001 2

1.761 9

no change

Xanthoxic acid

267.162 8

667.4

0.043 1

1.620 8

no change

Baicalein

271.179 7

702.9

0.000 0

1.909 4

no change

（5-L-Glutamyl）-L-glutamate

277.103 7

131.7

0.000 1

1.341 7

Sulfamethazine

279.092 6

749.0

0.040 8

1.030 1

no change

Guanosine

284.098 4

280.3

0.034 0

1.141 6

no change

9-OxoODE

295.225 6

867.6

0.008 8

2.429 9

no change

Enterolactone

299.126 8

594.6

0.002 1

1.547 7

no change

Dihydrocapsaicin

308.220 7

626.3

0.000 1

2.735 5

Moupinamide

314.123 7

174.4

0.019 1

1.143 0

down

no change

N-Acetylthienamycin

314.102 6

76.8

0.038 8

1.170 4

no change

down

no change

Oxycodone

316.154 1

510.0

0.027 2

1.497 7

no change

Clostebol

323.182 7

653.5

0.004 4

1.738 5

no cha nge

no change

Melibiose

325.112 6

322.2

0.015 2

2.389 3

no cha nge

no change

Bitertanol

338.194 7

732.1

0.001 0

2.094 7

no change

down

no change

17alpha，21-Dihydroxypregnenolone

349.235 9

563.2

0.012 0

1.706 2

no change

Cortisone

360.202 7

450.8

0.004 1

1.179 6

no change

Aldosterone

361.220 4

877.6

0.035 6

1.759 6

no change

18-Hydroxycorticosterone

363.214 7

546.5

0.023 3

1.170 0

no change

down

Tangeritin

373.127 5

794.1

0.000 0

1.097 4

down

no change

down

S-Adenosylmethionine

398.239 8

792.9

0.016 6

1.347 2

no change

N1，N8-Bis（4-coumaroyl）spermidine

438.240 2

489.8

0.003 8

1.191 6

down

no change

down

Creatinine

112.984 7

921.7

0.011 9

2.422 1

no change

5-Aminopentanoic acid

115.920 9

813.7

0.017 1

1.614 0

no change

down

Citramalic acid

129.018 8

142.0

0.001 0

1.893 8

down

no change

down

Glycyl-glycine

132.048 9

177.9

0.034 7

1.877 3

no change

down

Adenine

134.047 4

250.6

0.034 4

1.943 5

no change

3-Dehydro-L-threonate

134.024 9

452.7

0.001 3

1.297 0

down

no change

down

Threonic acid

135.030 1

118.1

0.043 1

1.451 5

no change

Dimethylbenzimidazole

145.040 8

431.2

0.005 8

2.076 3

no change

D-Glutamine

145.062 2

88.5

0.017 8

1.212 3

no change

3-Aminopentanedioate

146.046 0

94.3

0.000 9

1.252 4

no change

6-Methyladenine

148.063 0

350.2

0.009 5

1.673 5

no change

D-Xylose

149.045 7

93.0

0.015 5

1.286 7

no change

（R）-Mandelamide

151.060 6

983.4

0.011 8

1.356 9

no change

down

no change

3-Hydroxyvalproic acid

159.102 6

331.4

0.030 8

1.513 1

no change

Oxoadipic acid

160.040 6

454.3

0.022 4

2.288 4

no change

Umbelliferone

161.024 5

533.1

0.048 6

2.446 7

no change

L-Phenylalanine

164.071 8

304.9

0.008 4

1.220 6

no change

6-Methylmercaptopurine

165.021 0

142.5

0.001 0

1.642 3

no change

Terephthalate

165.019 7

388.4

0.022 1

1.642 2

no change

Hydantoin-5-propionic acid

171.041 4

95.7

0.018 2

1.498 5

no change

N-Acetylleucine

172.098 0

340.4

0.017 4

1.108 7

no change

Allantoic acid

175.048 3

82.7

0.000 1

1.035 9

down

no change

2-Dehydro-D-glucono-1，5-lactone

176.035 3

206.6

0.001 2

1.209 1

no change

down

no change

D-Mannonate

177.040 5

81.4

0.002 7

1.195 3

no change

down

no change

4-Hydroxyphenylpyruvic acid

179.035 2

303.3

0.000 4

1.048 9

no change

D-Mannose

179.056 4

90.1

0.012 9

1.120 3

no change

Homovanillate

181.050 7

164.0

0.021 2

2.061 9

no change

Hydroxyphenyllactic acid

181.050 5

253.8

0.000 0

2.968 4

no change

2＇，6＇-Dihydroxy-4＇-methoxyacetophenone

181.050 6

426.9

0.033 6

1.037 9

no change

10-Oxodecanoate

186.121 9

459.7

0.003 8

1.003 1

no change

down

no change

trans-Ferulic acid

193.050 8

296.6

0.000 1

1.614 6

down

Galactaric acid

209.030 2

77.5

0.001 7

1.450 4

no change

Milrinone

210.067 1

609.4

0.004 5

1.762 7

no change

Tridecanoic acid

214.108 6

393.8

0.050 0

2.001 8

no change

down

N-Acetyl-D-glucosamine

221.154 8

855.3

0.010 5

1.773 0

no change

Aciclovir

225.080 3

425.4

0.006 0

1.062 3

down

no change

down

Xylitol 5-phosphate

231.027 7

100.4

0.024 8

1.257 3

no change

Equol

241.087 2

685.9

0.003 2

1.631 0

no change

down

no change

Uridine

243.061 8

166.7

0.019 9

2.366 6

down

no change

Pyridoxal phosphate

247.028 0

317.9

0.011 7

1.148 0

no change

Shikimate 3-phosphate

253.017 8

470.8

0.003 9

2.324 5

no change

down

Palmitic acid

255.233 1

874.8

0.002 3

1.503 0

no change

Zidovudine

267.090 7

459.3

0.000 0

1.243 5

Norizalpinin

269.045 6

471.3

0.013 3

1.542 7

no change

down

no change

3＇-Hydroxydaidzein

269.045 5

537.3

0.011 1

1.040 4

no change

Arbutin

272.095 7

569.0

0.004 3

2.042 9

down

no change

down

beta-D-3-Ribofuranosyluric acid

281.053 9

128.2

0.021 9

1.251 5

no change

Dihydrotestosterone

289.165 9

322.0

0.000 0

1.042 4

no change

Kaempferide

299.056 3

687.9

0.000 1

1.744 2

n o change

no change

Morin

301.037 7

369.6

0.036 2

1.052 9

down

no change

（S，E）-Zearalenone

317.139 2

787.7

0.001 7

2.381 2

no change

GMP

344.039 7

149.6

0.001 8

1.044 0

no change

down

Pirenzepine

350.163 4

521.1

0.000 0

1.605 7

no change

down

Sinigrin

359.033 7

419.2

0.000 0

2.481 8

no change

Deoxycholic acid

392.288 1

790.8

0.019 7

1.005 2

no change

Carvedilol

405.189 0

563.4

0.021 2

1.369 0

down

no change

Allocholic acid

407.281 7

677.7

0.031 1

1.169 0

down

no change

Daidzin

415.101 5

491.3

0.040 8

1.823 3

no change

Astragalin

448.108 5

464.7

0.028 8

2.674 4

no ch ange

no change