中国药学杂志

Heating rate/℃·min^-1	T/℃	t/min
0	30	5
3	40	4
5	60	2
10	80	2
10	110	3
5	120	2
5	144	0
3	180	0
8	280	1
5	300	0

Heating rate/℃·min^-1	T/℃	t/min
0	30	5
3	40	4
5	60	2
10	80	2
10	110	3
5	120	2
5	144	0
3	180	0
8	280	1
5	300	0

No.	t_R	Library /ID	CAS	Match	Relative Content/%
1	19.98	Phenol	108-95-2	95	1.47	0.23	2.95
2	23.21	2-methyl-Phenol	95-48-7	98	-	-	0.45
3	24.10	p-Cresol	106-44-5	92	0.38	-	0.40
4	24.55	2-methoxy-guaiacol	90-05-1	96	1.68	-	5.98
5	27.72	4-ethyl-phenol	123-07-9	95	1.84	-	1.16
6	28.61	Creosol	93-51-6	89	-	-	0.89
7	28.65	6-methoxy-m-cresol	1195-09-1	83	1.02	-	-
8	32.12	4-ethyl-2-methoxy-phenol	2785-89-9	91	-	-	1.59
9	33.53	4-hydroxy-3-methoxystyrene	7786-61-0	93	1.44	-	1.46
10	35.22	2,6-dimethoxy-syringol	91-10-1	97	2.22	-	6.96
11	35.50	Eugenol	97-53-0	95	-	-	0.25
12	35.91	2-methoxy-4-propyl-dihydroeugenol	2785-87-7	96	-	-	0.16
13	39.00	trans-Isoeugenol	5932-68-3	98	-	-	1.55
14	41.21	2,4-di-t-butylphenol	96-76-4	91	1.53	1.83	0.32
15	44.30	2,6-dimethoxy-4-allylphenol	6627-88-9	89	0.19	-	0.54
16	61.94	2,2'-methylenebis(6-tert-butyl-4-methylphenol)	119-47-1	96	0.16	1.59	0.11
17	12.66	5-methyl-alpha-angelica lactone	591-12-8	80	-	-	0.14
18	13.22	diacetate glycol diacetate	111-55-7	88	1.77	-	1.73
19	15.68	4-hydroxy-butanoic acid	591-81-1	83	0.81	-	2.03
20	15.47	Butyrolactone	96-48-0	87	1.32	-	2.14
21	15.78	Methyl acetoxyacetate	5837-80-9	85	-	-	0.35
22	19.48	Methyl 2-furoate	611-13-2	90	-	-	0.49
23	20.20	Methyl 4-oxopentanoate	624-45-3	87	-	-	0.42
24	20.46	Furan-2-ylmethyl acetate	623-17-6	97	-	-	2.20
25	42.19	Methyl Laurate	111-82-0	96	-	2.63	-
26	54.70	Methyl palmitate	112-39-0	97	-	4.08	-
27	58.15	Methyl stearate	112-61-8	99	-	2.53	-
28	4.62	Acetoin	513-86-0	86	-	-	0.22
29	6.73	1-Hydroxy-2-butanone	5077-67-8	82	-	-	1.68
30	6.85	Carbamic acid,	79069-13-9	92	0.82	-	0.77
31	7.76	Cyclopentanone	120-92-3	86	-	-	0.11
32	8.61	2-methyl-tetrahydrofuran-3-one	3188-00-9	90	-	-	0.57
33	13.19	2-Propanone, 1-(acetyloxy)-1-acetoxyacetone	592-20-1	81	4.89	-	-
34	13.82	2-cyclopentene-1, 4-dione	930-60-9	86	-	-	0.21
35	19.16	1-acetory-2-butanone	1575-57-1	90	-	-	1.08
36	25.57	Maltol	118-71-8	98	-	-	1.07
37	10.05	Furfural	98-01-1	95	14.27	-	16.26
38	18.67	5-methyl-2-furaldehyde	620-02-0	97	0.74	-	1.64
39	20.99	2 Formyl-1H-pyrrole	1003-29-8	87	-	-	0.20
40	35.64	4-hydroxy-benzaldehyde	123-08-0	92	-	1.11	0.85
41	37.14	Vanillin	121-33-5	90	-	-	0.17
42	46.24	4-hydroxy-3,5-dimethoxy-syringaldehyde	134-96-3	96	-	-	0.05
43	48.67	3-(4-hydroxy-3-methoxyphenyl)-coniferyl aldehyde	458-36-6	93	-	-	0.09
44	4.34	Propanoic acid	79-09-4	81	-	-	0.26
45	7.91	Butanoic acid	107-92-6	87	-	-	0.06
46	41.81	Homovanillic acid	306-08-1	87	-	-	0.22
47	11.81	2-Furanmethanol	98-00-0	98	9.25	0.27	7.69
48	9.41	methylpyrazine	109-08-0	90	-	-	0.31
49	10.45	hexamethyl-Cyclotrisiloxane	541-05-9	90	-	5.07	-
50	20.86	Isobutyric acid anhydride	97-72-3	84	-	-	3.17
51	21.39	octamethyl-Cyclotetrasiloxane	556-67-2	91	-	2.75	-
52	29.62	2,3-dihydro-coumaran	496-16-2	94	8.46	-	4.11
53	41.45	tetradecamethyl-Cycloheptasiloxane	107-50-6	93	-	5.39	-
54	61.20	(Z)-oleamide	301-02-0	96	0.38	5.72	0.80

No.	t_R	Library /ID	CAS	Match	Relative Content/%
1	19.98	Phenol	108-95-2	95	1.47	0.23	2.95
2	23.21	2-methyl-Phenol	95-48-7	98	-	-	0.45
3	24.10	p-Cresol	106-44-5	92	0.38	-	0.40
4	24.55	2-methoxy-guaiacol	90-05-1	96	1.68	-	5.98
5	27.72	4-ethyl-phenol	123-07-9	95	1.84	-	1.16
6	28.61	Creosol	93-51-6	89	-	-	0.89
7	28.65	6-methoxy-m-cresol	1195-09-1	83	1.02	-	-
8	32.12	4-ethyl-2-methoxy-phenol	2785-89-9	91	-	-	1.59
9	33.53	4-hydroxy-3-methoxystyrene	7786-61-0	93	1.44	-	1.46
10	35.22	2,6-dimethoxy-syringol	91-10-1	97	2.22	-	6.96
11	35.50	Eugenol	97-53-0	95	-	-	0.25
12	35.91	2-methoxy-4-propyl-dihydroeugenol	2785-87-7	96	-	-	0.16
13	39.00	trans-Isoeugenol	5932-68-3	98	-	-	1.55
14	41.21	2,4-di-t-butylphenol	96-76-4	91	1.53	1.83	0.32
15	44.30	2,6-dimethoxy-4-allylphenol	6627-88-9	89	0.19	-	0.54
16	61.94	2,2'-methylenebis(6-tert-butyl-4-methylphenol)	119-47-1	96	0.16	1.59	0.11
17	12.66	5-methyl-alpha-angelica lactone	591-12-8	80	-	-	0.14
18	13.22	diacetate glycol diacetate	111-55-7	88	1.77	-	1.73
19	15.68	4-hydroxy-butanoic acid	591-81-1	83	0.81	-	2.03
20	15.47	Butyrolactone	96-48-0	87	1.32	-	2.14
21	15.78	Methyl acetoxyacetate	5837-80-9	85	-	-	0.35
22	19.48	Methyl 2-furoate	611-13-2	90	-	-	0.49
23	20.20	Methyl 4-oxopentanoate	624-45-3	87	-	-	0.42
24	20.46	Furan-2-ylmethyl acetate	623-17-6	97	-	-	2.20
25	42.19	Methyl Laurate	111-82-0	96	-	2.63	-
26	54.70	Methyl palmitate	112-39-0	97	-	4.08	-
27	58.15	Methyl stearate	112-61-8	99	-	2.53	-
28	4.62	Acetoin	513-86-0	86	-	-	0.22
29	6.73	1-Hydroxy-2-butanone	5077-67-8	82	-	-	1.68
30	6.85	Carbamic acid,	79069-13-9	92	0.82	-	0.77
31	7.76	Cyclopentanone	120-92-3	86	-	-	0.11
32	8.61	2-methyl-tetrahydrofuran-3-one	3188-00-9	90	-	-	0.57
33	13.19	2-Propanone, 1-(acetyloxy)-1-acetoxyacetone	592-20-1	81	4.89	-	-
34	13.82	2-cyclopentene-1, 4-dione	930-60-9	86	-	-	0.21
35	19.16	1-acetory-2-butanone	1575-57-1	90	-	-	1.08
36	25.57	Maltol	118-71-8	98	-	-	1.07
37	10.05	Furfural	98-01-1	95	14.27	-	16.26
38	18.67	5-methyl-2-furaldehyde	620-02-0	97	0.74	-	1.64
39	20.99	2 Formyl-1H-pyrrole	1003-29-8	87	-	-	0.20
40	35.64	4-hydroxy-benzaldehyde	123-08-0	92	-	1.11	0.85
41	37.14	Vanillin	121-33-5	90	-	-	0.17
42	46.24	4-hydroxy-3,5-dimethoxy-syringaldehyde	134-96-3	96	-	-	0.05
43	48.67	3-(4-hydroxy-3-methoxyphenyl)-coniferyl aldehyde	458-36-6	93	-	-	0.09
44	4.34	Propanoic acid	79-09-4	81	-	-	0.26
45	7.91	Butanoic acid	107-92-6	87	-	-	0.06
46	41.81	Homovanillic acid	306-08-1	87	-	-	0.22
47	11.81	2-Furanmethanol	98-00-0	98	9.25	0.27	7.69
48	9.41	methylpyrazine	109-08-0	90	-	-	0.31
49	10.45	hexamethyl-Cyclotrisiloxane	541-05-9	90	-	5.07	-
50	20.86	Isobutyric acid anhydride	97-72-3	84	-	-	3.17
51	21.39	octamethyl-Cyclotetrasiloxane	556-67-2	91	-	2.75	-
52	29.62	2,3-dihydro-coumaran	496-16-2	94	8.46	-	4.11
53	41.45	tetradecamethyl-Cycloheptasiloxane	107-50-6	93	-	5.39	-
54	61.20	(Z)-oleamide	301-02-0	96	0.38	5.72	0.80

Library /ID	FR vs DD	FR vs RE	RE vs DD
Phenol	1.170	0.000	-	-	1.153	0.000
2-methoxy-Phenol	-	-	1.214	0.002	1.738	0.000
4-ethyl-2-methoxy-Phenol	1.319	0.004	-	-	-	-
2,6-dimethoxy-syringol	2.326	0.001	-	-	1.898	0.000
trans-Isoeugenol	1.344	0.002	-	-	-	-
2,4-di-t-butylphenol	1.108	0.000	-	-	-	-
4-hydroxy-butanoic acid	1.102	0.002	-	-	1.010	0.000
Butyrolactone	-	-	-	-	1.010	0.000
Furan-2-ylmethyl-acetate	1.598	0.002	-	-	1.051	0.002
1-Hydroxy-2-butanone	1.377	0.003	-	-	-	-
1-(acetyloxy)-2-Butanone	1.102	0.004	-	-	-	-
Maltol	1.051	0.005	-	-	-	-
Furfural	1.180	0.001	2.158	0.002	2.915	0.000
2-Furanmethanol	1.301	0.000	1.738	0.001	1.956	0.000
Isobutyric acid anhydride	1.895	0.003	-	-	1.246	0.003
2,3-dihydro-coumaran	2.188	0.001	1.640	0.002	1.450	0.000
(Z)-oleamide	-	-	1.284	0.001	1.563	0.011

Library /ID	FR vs DD	FR vs RE	RE vs DD
Phenol	1.170	0.000	-	-	1.153	0.000
2-methoxy-Phenol	-	-	1.214	0.002	1.738	0.000
4-ethyl-2-methoxy-Phenol	1.319	0.004	-	-	-	-
2,6-dimethoxy-syringol	2.326	0.001	-	-	1.898	0.000
trans-Isoeugenol	1.344	0.002	-	-	-	-
2,4-di-t-butylphenol	1.108	0.000	-	-	-	-
4-hydroxy-butanoic acid	1.102	0.002	-	-	1.010	0.000
Butyrolactone	-	-	-	-	1.010	0.000
Furan-2-ylmethyl-acetate	1.598	0.002	-	-	1.051	0.002
1-Hydroxy-2-butanone	1.377	0.003	-	-	-	-
1-(acetyloxy)-2-Butanone	1.102	0.004	-	-	-	-
Maltol	1.051	0.005	-	-	-	-
Furfural	1.180	0.001	2.158	0.002	2.915	0.000
2-Furanmethanol	1.301	0.000	1.738	0.001	1.956	0.000
Isobutyric acid anhydride	1.895	0.003	-	-	1.246	0.003
2,3-dihydro-coumaran	2.188	0.001	1.640	0.002	1.450	0.000
(Z)-oleamide	-	-	1.284	0.001	1.563	0.011

Group	Library/ID
“DD vs FR”vs“DD vs RE”	2-Furanmethanol, acetate³⁾; Propanoic acid, 2-methyl-, anhydride³⁾; Phenol¹⁾²⁾³⁾; 2-Furanmethanol¹⁾²⁾³⁾
“FR vs RE”vs“FR vs DD”	Furfural¹⁾³⁾; 2,3-dihydro-¹⁾³⁾; 2-Furanmethanol¹⁾²⁾³
“RE vs FR”vs“RE vs DD”	Phenol, 2-methoxy-¹⁾³⁾; Furfural¹⁾³⁾; 2,3-dihydro-¹⁾³⁾; 9-Octadecenamide, (Z)-¹⁾²⁾³⁾; 2-Furanmethanol¹⁾²⁾³⁾
“RE”vs“FR”vs“DD”	2-Furanmethanol¹⁾²⁾³⁾; Furfural¹⁾³⁾; Benzofuran, 2,3-dihydro-¹⁾³⁾

Group	Library/ID
“DD vs FR”vs“DD vs RE”	2-Furanmethanol, acetate³⁾; Propanoic acid, 2-methyl-, anhydride³⁾; Phenol¹⁾²⁾³⁾; 2-Furanmethanol¹⁾²⁾³⁾
“FR vs RE”vs“FR vs DD”	Furfural¹⁾³⁾; 2,3-dihydro-¹⁾³⁾; 2-Furanmethanol¹⁾²⁾³
“RE vs FR”vs“RE vs DD”	Phenol, 2-methoxy-¹⁾³⁾; Furfural¹⁾³⁾; 2,3-dihydro-¹⁾³⁾; 9-Octadecenamide, (Z)-¹⁾²⁾³⁾; 2-Furanmethanol¹⁾²⁾³⁾
“RE”vs“FR”vs“DD”	2-Furanmethanol¹⁾²⁾³⁾; Furfural¹⁾³⁾; Benzofuran, 2,3-dihydro-¹⁾³⁾

Process	Phenol/mg·mL^-1	Phenol, 2-methoxyphenol/mg·mL^-1
FR	0.031±0.002	ND
RE	ND	ND
DD	0.097±0.004	0.150±0.017

Process	Phenol/mg·mL^-1	Phenol, 2-methoxyphenol/mg·mL^-1
FR	0.031±0.002	ND
RE	ND	ND
DD	0.097±0.004	0.150±0.017

Group	m(0 d)/g	m(7 d)/g	m(14 d)/g
NC(♂)	23.2±1.16	36.3±2.23	41.9±3.67
NC(♀)	23.1±0.92	30.3±2.61	36.7±4.01
FR(♂)	23.9±1.94	35.3±2.52	42.2±2.67
FR(♀)	22.8±1.51	30.4±2.33	34.9±3.17
RE(♂)	22.8±1.43	34.7±3.36	40.6±4.04
RE(♀)	23.5±1.22	29.7±2.33	35.3±5.21
DD(♂)	22.3±1.62	26.9±3.34¹⁾	29.1±5.86¹⁾
DD(♀)	23.1±0.88	24.3±2.49¹⁾	26.5±3.19¹⁾

Group	m(0 d)/g	m(7 d)/g	m(14 d)/g
NC(♂)	23.2±1.16	36.3±2.23	41.9±3.67
NC(♀)	23.1±0.92	30.3±2.61	36.7±4.01
FR(♂)	23.9±1.94	35.3±2.52	42.2±2.67
FR(♀)	22.8±1.51	30.4±2.33	34.9±3.17
RE(♂)	22.8±1.43	34.7±3.36	40.6±4.04
RE(♀)	23.5±1.22	29.7±2.33	35.3±5.21
DD(♂)	22.3±1.62	26.9±3.34¹⁾	29.1±5.86¹⁾
DD(♀)	23.1±0.88	24.3±2.49¹⁾	26.5±3.19¹⁾

Group	m(0 d)/g	m(7 d)/g	m(14 d)/g	m(21 d)/g	m(28 d)/g
NC(♂)	285.4	±8.89	342.3	±11.71	364.7	±13.54	405.1	±18.12	429.8	±19.40
NC(♀)	267.3	±7.36	322.4	±12.34	332.8	±16.57	378.2	±19.33	385.3	±18.74
DL(♂)	285.8	±9.68	343.7	±14.37	371.5	±18.54	412.5	±24.00	436.3	±27.79
DL(♀)	271.2	±8.22	318.3	±13.43	339.8	±16.41	364.5	±21.13	390.2	±20.63
DM(♂)	285.6	±9.00	335.2	±29.95	350.1	±39.59	387.8	±43.78	403.2	±53.39
DM(♀)	271.5	±10.23	324.3	±17.46	329.5	±12.95	354.9	±27.80	381.2	±32.21
DH(♂)	285.5	±6.04	334.9	±22.36	364.2	±31.24	397.9	±36.53	405.4	±37.66
DH(♀)	268.4	±7.38	318.3	±15.39	325.3	±12.95	360.1	±33.51	379.9	±42.81

Group	m(0 d)/g	m(7 d)/g	m(14 d)/g	m(21 d)/g	m(28 d)/g
NC(♂)	285.4	±8.89	342.3	±11.71	364.7	±13.54	405.1	±18.12	429.8	±19.40
NC(♀)	267.3	±7.36	322.4	±12.34	332.8	±16.57	378.2	±19.33	385.3	±18.74
DL(♂)	285.8	±9.68	343.7	±14.37	371.5	±18.54	412.5	±24.00	436.3	±27.79
DL(♀)	271.2	±8.22	318.3	±13.43	339.8	±16.41	364.5	±21.13	390.2	±20.63
DM(♂)	285.6	±9.00	335.2	±29.95	350.1	±39.59	387.8	±43.78	403.2	±53.39
DM(♀)	271.5	±10.23	324.3	±17.46	329.5	±12.95	354.9	±27.80	381.2	±32.21
DH(♂)	285.5	±6.04	334.9	±22.36	364.2	±31.24	397.9	±36.53	405.4	±37.66
DH(♀)	268.4	±7.38	318.3	±15.39	325.3	±12.95	360.1	±33.51	379.9	±42.81

Group	Heart index/%	Liver index/%	Spleen index/%	Lung index/%	Kidney index/%
NC(♂)	0.32	±0.02	2.65	±0.14	0.21	±0.01	0.36	±0.08	0.62	±0.15
NC(♀)	0.29	±0.03	2.42	±0.15	0.18	±0.01	0.33	±0.06	0.52	±0.21
DL(♂)	0.30	±0.01	2.58	±0.14	0.22	±0.04	0.32	±0.06	0.64	±0.03
DL(♀)	0.28	±0.02	2.47	±0.18	0.17	±0.03	0.30	±0.05	0.53	±0.19
DM(♂)	0.31	±0.02	2.62	±0.23	0.22	±0.05	0.36	±0.05	0.69	±0.03
DM(♀)	0.29	±0.01	2.51	±0.17	0.18	±0.04	0.34	±0.08	0.61	±0.04
DH(♂)	0.36	±0.04¹⁾	3.19	±0.45¹⁾	0.22	±0.01	0.44	±0.06¹⁾	0.75	±0.06¹⁾
DH(♀)	0.33	±0.05¹⁾	2.91	±0.33¹⁾	0.19	±0.03	0.41	±0.07¹⁾	0.70	±0.04¹⁾

Group	Heart index/%	Liver index/%	Spleen index/%	Lung index/%	Kidney index/%
NC(♂)	0.32	±0.02	2.65	±0.14	0.21	±0.01	0.36	±0.08	0.62	±0.15
NC(♀)	0.29	±0.03	2.42	±0.15	0.18	±0.01	0.33	±0.06	0.52	±0.21
DL(♂)	0.30	±0.01	2.58	±0.14	0.22	±0.04	0.32	±0.06	0.64	±0.03
DL(♀)	0.28	±0.02	2.47	±0.18	0.17	±0.03	0.30	±0.05	0.53	±0.19
DM(♂)	0.31	±0.02	2.62	±0.23	0.22	±0.05	0.36	±0.05	0.69	±0.03
DM(♀)	0.29	±0.01	2.51	±0.17	0.18	±0.04	0.34	±0.08	0.61	±0.04
DH(♂)	0.36	±0.04¹⁾	3.19	±0.45¹⁾	0.22	±0.01	0.44	±0.06¹⁾	0.75	±0.06¹⁾
DH(♀)	0.33	±0.05¹⁾	2.91	±0.33¹⁾	0.19	±0.03	0.41	±0.07¹⁾	0.70	±0.04¹⁾

Group	WBC/×10⁹·L^-1	RBC/×10¹²·L^-1	HGB/g·L^-1	PLT/×10⁹·L^-1	MCH/×10^-6 μg	MPV/×10^-15 L	EO/%
NC(♂+♀)	6.72±0.92	7.66±0.39	148.57±6.34	943.14±115.37	19.4±0.46	6.79±0.17	1.01±0.27
DL(♂+♀)	7.40±1.25	7.85±0.40	152.25±6.31	1022.13±113.15	19.44±0.71	6.91±0.18	1.81±1.03
DM(♂+♀)	6.77±1.81	8.19±0.40	155.86±5.69	965.57±259.54	19.03±0.72	7.07±0.26	2.93±2.71¹⁾
DH(♂+♀)	7.43±4.31	8.71±0.90¹⁾	166.17±16.91¹⁾	1 001.67±258.88	19.10±0.47	7.12±0.18¹⁾	0.88±0.54

Group	WBC/×10⁹·L^-1	RBC/×10¹²·L^-1	HGB/g·L^-1	PLT/×10⁹·L^-1	MCH/×10^-6 μg	MPV/×10^-15 L	EO/%
NC(♂+♀)	6.72±0.92	7.66±0.39	148.57±6.34	943.14±115.37	19.4±0.46	6.79±0.17	1.01±0.27
DL(♂+♀)	7.40±1.25	7.85±0.40	152.25±6.31	1022.13±113.15	19.44±0.71	6.91±0.18	1.81±1.03
DM(♂+♀)	6.77±1.81	8.19±0.40	155.86±5.69	965.57±259.54	19.03±0.72	7.07±0.26	2.93±2.71¹⁾
DH(♂+♀)	7.43±4.31	8.71±0.90¹⁾	166.17±16.91¹⁾	1 001.67±258.88	19.10±0.47	7.12±0.18¹⁾	0.88±0.54

Group	Glu /mmol·L^-1	ALT /U·L^-1	AST /U·L^-1	TP /g·L^-1	ALB /g·L^-1	TG /mmol·L^-1	TC /mmol·L^-1	CREA /μmol·L^-1	UREA /mmol·L^-1
NC(♂+♀)	4.92	±0.88	44.68	±7.29	108.58	±15.11	65.54	±2.13	32.9	±0.71	0.81	±0.32	1.81	±0.30	29.98	±2.51	6.61	±0.55
DL(♂+♀)	4.55	±0.95	34.64	±21.35	117.84	±18.33	62.31	±2.53	30.92	±1.50	0.60	±0.31	1.72	±0.27	23.16	±16.54	5.44	±3.01
DM(♂+♀)	4.82	±0.82	58.12	±25.47	140.96	±37.08	65.18	±1.68	32.18	±0.69	0.79	±0.36	1.74	±0.22	30.82	±8.14	6.37	±0.64
DH(♂+♀)	7.55	±7.68	52.84	±14.76	120.94	±43.56	73.82	±9.00¹⁾	29.5	±16.60	0.55	±0.20	1.55	±0.90	25.74	±3.48	6.01	±1.70

Group	Glu /mmol·L^-1	ALT /U·L^-1	AST /U·L^-1	TP /g·L^-1	ALB /g·L^-1	TG /mmol·L^-1	TC /mmol·L^-1	CREA /μmol·L^-1	UREA /mmol·L^-1
NC(♂+♀)	4.92	±0.88	44.68	±7.29	108.58	±15.11	65.54	±2.13	32.9	±0.71	0.81	±0.32	1.81	±0.30	29.98	±2.51	6.61	±0.55
DL(♂+♀)	4.55	±0.95	34.64	±21.35	117.84	±18.33	62.31	±2.53	30.92	±1.50	0.60	±0.31	1.72	±0.27	23.16	±16.54	5.44	±3.01
DM(♂+♀)	4.82	±0.82	58.12	±25.47	140.96	±37.08	65.18	±1.68	32.18	±0.69	0.79	±0.36	1.74	±0.22	30.82	±8.14	6.37	±0.64
DH(♂+♀)	7.55	±7.68	52.84	±14.76	120.94	±43.56	73.82	±9.00¹⁾	29.5	±16.60	0.55	±0.20	1.55	±0.90	25.74	±3.48	6.01	±1.70

干馏制鲜竹沥饮片差异成分分析及其关联的安全性评价

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唐铭霞 ¹^,² , 徐焕华 ¹^,²^,^* , 张雨恬 ¹^,³ , 曾慧敏 ¹^,² , 伍振峰 ¹^,² , 杨明 ¹^,²^,^*

中国药学杂志 | 研究论文 2024,59(6): 501-510

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中国药学杂志 | 研究论文 2024, 59(6): 501-510

干馏制鲜竹沥饮片差异成分分析及其关联的安全性评价

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唐铭霞¹^,², 徐焕华¹^,²^,^*, 张雨恬¹^,³, 曾慧敏¹^,², 伍振峰¹^,², 杨明¹^,²^,^*

作者信息

¹ 江西中医药大学现代中药制剂教育部重点实验室, 南昌 330004

² 江西中医药大学经典名方现代中药创制全国重点实验室, 南昌 330004

³ 江西中医药大学附属医院, 南昌 330004

唐铭霞,女,硕士研究生研究方向:中药药剂与药理研究

通讯作者:

^*徐焕华,男,副教授研究方向:中药药理与毒理 Tel:(0791)87119032;杨明,男,教授研究方向:中药炮制及药剂研究 Tel:(0791)87119118

Analysis of Different Components and Their Associated Safety Evaluation of Succus Bambusae Prepared by Dry Distillation Process

Mingxia TANG¹^,², Huanhua XU¹^,²^,^*, Yutian ZHANG¹^,³, Huimin ZENG¹^,², Zhenfeng WU¹^,², Ming YANG¹^,²^,^*

Affiliations

¹ Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China

² State Key Laboratory of Innovative Medicine and High Efficiency and Energy Saving Pharmaceutical Equipment, Jiangxi University of Chinese Medicine, Nanchang 330004, China

³ The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang 330004, China

出版时间: 2024-03-22 doi: 10.11669/cpj.2024.06.005

文章导航

摘要

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目的通过比较干馏制鲜竹沥与传统工艺鲜竹沥饮片的物质成分差异,进一步从急性毒性和亚急性毒性角度分析干馏制鲜竹沥饮片的安全性,并将成分差异和安全性进行关联分析。为干馏制鲜竹沥大品种的工艺规范化和质量标准的进一步提升提供数据支撑。方法采用气相色谱质谱联用(GC-MS)方法、结合主成分分析(PCA)和正交偏最小乘法判别分析(OPLS-DA)数学算法,分析得到三种工艺的差异性成分以及独有成分,进一步采用HPLC方法对安全性相关指标进行定量分析。采用急性毒性试验和亚急性毒性试验相结合的方案对安全性进行评估。结果分析表明,从不同工艺鲜竹沥中共归属了47种成分,包括酚类16种、酮类11种、酯类9种、醛类7种、羧酸类3种、醇类1种,相对含量和物质种类具有明显改变。对安全性相关成分苯酚和愈创木酚定量分析结果显示,干馏与火烤工艺中均检出苯酚和愈创木酚,含量分别为(0.097±0.004)和(0.150±0.017) mg·mL^-1。急性毒性试验结果表明,干馏制鲜竹沥饮片对小鼠体重和胃肠道存在不良影响。亚急性毒性试验结果与急性毒性试验结果具有一致性。干馏制鲜竹沥高剂量组对胃肠道组织存在不良影响,心、肝、肺和肾脏器指数也显著升高,但低、中剂量组未产生不良效应。结论干馏制鲜竹沥饮片物质基础的不同确实存在安全性风险,且关联分析表明该风险为苯酚及愈创木酚等具有刺激性的酚类成分所致。但综合来说,安全性评价提示干馏制鲜竹沥饮片总体安全性较好。这为鲜竹沥饮片的临床应用提供了毒理学数据支撑。

关键词

鲜竹沥 / 干馏 / 物质基础 / 安全性评价 / 愈创木酚

Abstract

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OBJECTIVE To compare the differences in the chemical compositionof Succus Bambusae with different processes,analyze the safety of Succus Bambusae produced by dry distillation from theperspectives of acuteand subacute toxiciy and provide data support for the further improvement ofthe process standardization andquality standards ofthe large variety offresh bamboo distillate. METHODS Using GC-MS method, combined with PCA and OPLS-DA mathematical algorithms, the differential components and unique components among the three processes were analyzed, and the HPLC method was used to quantitatively analyze the indicators related to toxicity potential. Toxic potential was assessed using a combined acute and subacute toxicity protocol. RESULTS Relative content and substance types have changed significantly, total of 47 components were identified from different processes of Succus Bambusae, including 16 phenols, 11 ketones, 9 esters, 7 aldehydes, 3 carboxylic acids, and 1 alcohol. The results of quantitative analysis of phenol and guaiacol showed that only phenol and guaiacol were detected in the dry distillation process, and the contents were (0.097±0.004) and (0.150±0.017)mg·mL^-1 respectively. The results of acute toxicity test showed that dry distillation of Succus Bambusae decoction had adverse effects on the body weight and gastrointestinal tract of mice. The subacute toxicity test results are consistent with the acute toxicity test results. The high-dose group of dry-distilled Succus Bambusae had adverse effects on the gastrointestinal tract tissue, and the organ indexes of heart, liver, lung and kidney were also significantly increased, but no adverse effects appeared in the low-dose and middle-dose groups. CONCLUSION The huge difference in the material basis of dry distillation Succus Bambusae does have safety risks, and the correlation analysis shows that the risk factors are irritating phenolic components such as phenol and guaiacol. However, the safety evaluation indicates that dry distillation of Succus Bambusae is generally safer. This paper could provide toxicological data support for the clinical application of Succus Bambusae and its preparations.

Key words

Succus Bambusae / dry-distilled / material basis / safety evaluation / guaiacol

引用本文

唐铭霞, 徐焕华, 张雨恬, 曾慧敏, 伍振峰, 杨明. 干馏制鲜竹沥饮片差异成分分析及其关联的安全性评价. 中国药学杂志, 2024 , 59 (6) : 501 -510 . DOI: 10.11669/cpj.2024.06.005

Mingxia TANG, Huanhua XU, Yutian ZHANG, Huimin ZENG, Zhenfeng WU, Ming YANG. Analysis of Different Components and Their Associated Safety Evaluation of Succus Bambusae Prepared by Dry Distillation Process[J]. Chinese Pharmaceutical Journal, 2024 , 59 (6) : 501 -510 . DOI: 10.11669/cpj.2024.06.005

正文

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鲜竹沥又名竹沥、竹汁、竹油,最早于汉代《神农本草经》^[1]中被记载为“竹汁”,为禾本科植物粉绿竹(Phyllostachys glauca McClure)、净竹(Phyllostachys nuda McClure)及同属数种植物的鲜茎秆加热后自然沥出的液体^[2],被中医誉为“痰家圣剂”。鲜竹沥是我国沿用千年的传统药,最早可以追溯到梁代陶弘景的《名医别录》^[3]和《本草经集注》^[4],谓其“治暴中风,风痹,胸中大热,止烦闷”。现代研究表明鲜竹沥的化学成分复杂,主要有黄酮类、酸酚类、氨基酸类及无机元素(钙、铁、锰、锌等)^[5],具有清热祛痰、开窍定惊等疗效。临床上常单用或联用其他药物用于治疗上呼吸道感染^[6-7]、支气管肺炎^[8-9]、痰热咳嗽^[10-11]、肺脓肿^[12]、祛痰^[13-14]以及预防术后肺部的并发症^[15-16],服药方式常为口服或雾化吸入^[7,16-17],其临床疗效独特,深受患者认可。

鲜竹沥饮片的古法工艺是火烤法,现市场流通的鲜竹沥饮片兼有火烤法和回流提取法。与这两种工艺相比,干馏制鲜竹沥饮片的物质基础发生较大变化^[18],容易伴生安全性风险,且这种风险尚未见文献评估和研究,因此干馏制鲜竹沥的安全性仍亟待探索;此外,新制订的鲜竹沥饮片质量标准虽已涵盖干馏工艺,但仍未能规避物质基础差异导致的效应结局(毒效或药效)不一致的风险。基于此,本研究通过比较干馏制鲜竹沥饮片与传统工艺鲜竹沥饮片的物质成分差异,进一步从急性毒性和亚急性毒性角度评估干馏制鲜竹沥饮片的安全性,并将成分差异和毒性潜能进行关联分析。研究结果可为鲜竹沥大品种的工艺规范化和质量标准的进一步提升提供数据支撑,这对鲜竹沥大品种的工艺优化和优效产业化具有重要价值。

1 材料与方法

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1.1 仪器和设备

LGJ-30FD真空冷冻干燥机(北京松原华兴科技发展有限公司);JEA5001电子天平(五海浦春计量仪器有限公司);LIPH-1-10TNP优普超纯水机(武汉优普仪器设备有限公司);SXKW数量控温电热套(北京市永光明医疗仪器有限公司);DMA-35密度计(奥地利安东帕公司);卧式干馏器(江西赫百康华制药设备有限公司);Agilent 7890A/5975C型气质联用色谱仪(美国安捷伦公司);HI1220型烘片机(上海徕卡仪器有限公司);RM2235型手动石蜡切片机(上海徕卡显微系统有限公司)。

1.2 药材与试剂

竹子采自江西省南昌市新建区梅岭风景区四季花谷的毛竹茎秆,经江西中医药大学杨明教授鉴定为禾本科植物毛竹[Phyllostachys heterocycla (Carr.) Mitford cv. Pubescens]的茎秆;糠醛(批号:CHB210222)、糠醇(批号:CHB210223)、5-甲基呋喃醛(批号:CHB210222)、苯酚(批号:CHB201205)、2,3-二氢苯并呋喃(批号:CHB210121)、4-乙基苯酚(批号:CHB210123)、4-甲基愈创木酚(批号:CHB210223)、对乙烯基愈创木酚(批号:CHB210111)、紫丁香醇(批号:CHB201107)均购自成都克洛玛生物科技有限公司;愈创木酚(中国食品药品检定研究院,批号:100491-201902);HE染色试剂盒(北京索莱宝科技有限公司)。

1.3 实验动物

SPF级昆明小鼠80只,雌雄各半,体质量18~22 g;SPF级SD大鼠80只,雌雄各半,体质量180~220 g(江西中医药大学实验动物科技中心,生产许可证号:SCXK(赣)2023-0001)。动物饲养于本校实验动物科技中心,室温控制在18~28 ℃,湿度40%~80%,自然节律光照。期间自由饮食饮水,适应性喂养1周后进行实验。实验动物环境使用许可证号:SYXK(赣)2022-0002;伦理审查批件号:JZLLSC20220004。

1.4 不同工艺鲜竹沥饮片样品的制备

3种工艺制备的鲜竹沥饮片已分别按卫生部部颁标准中药材第一册(1992)和江西省药品监督管理局发布的鲜竹沥中药饮片标准(2022)进行质量控制,3种工艺制备的鲜竹沥饮片均符合规定。

火烤法:取新鲜毛竹锯成长度约40 cm的竹片,两端除去竹节,用酒精灯加热中部,收集两端滴下的淡黄色汁液,无液体流出停止加热,置于4 ℃环境下保存。

回流提取法:将新鲜毛竹劈成长2 cm,宽1 cm大小的竹块,取一定量竹块置于圆底烧瓶,加入7倍量纯净水,使水没过竹片浸泡1 h,回流提取1 h,过滤;第二次加入5倍量纯净水,同操作提取1 h,过滤。混合两次提取液,置于4 ℃环境下保存。

干馏法:取新鲜毛竹锯成长度约40 cm的竹片,两端除去竹节,将其置于干馏装置内,固定温度为370 ℃,压力在0.4 MPa左右,接0.5 h后馏出液作为样品,置于4 ℃环境下保存。

1.5 不同工艺鲜竹沥饮片物质成分分析

1.5.1 供试品、对照品溶液的制备

取3种工艺制备所得的鲜竹沥各5 mL,用二氯甲烷萃取3次(5,5,5 mL),静置时间20 min,取下层清液,合并3次萃取溶液,再过0.45 μm微孔滤膜,置于4 ℃环境下保存。分别精密称取糠醛对照品、糠醇对照品、5-甲基呋喃醛对照品、苯酚对照品、2,3-二氢苯并呋喃对照品、愈创木酚对照品、4-乙基苯酚对照品、4-甲基愈创木酚对照品、对乙烯基愈创木酚对照品以及紫丁香醇对照品适量,加入二氯甲烷制成每1 mL含糠醛0.615 3 mg、糠醇0.581 2 mg、5-甲基呋喃醛0.566 7 mg、苯酚1.017 2 mg、2,3-二氢苯并呋喃0.552 2 mg、愈创木酚1.222 2 mg、4-乙基苯酚0.509 6 mg、4-甲基愈创木酚0.762 4 mg、对乙烯基愈创木酚0.572 4 mg、紫丁香醇0.485 6 mg的混合对照品溶液,置于4 ℃环境下保存。

1.5.2 气相色谱质谱联用(GC-MS)分析条件

气相条件:Agilent123-1334 DB-624(1.8 μm×320 μm×30 m)毛细管色谱柱;载气为He,流速1.0 mL·min^-1;进样口温度280 ℃;分流比5∶1,进样量为1.0 μL,起始温度为30 ℃。

质谱条件:四极杆温度150 ℃;电离源为标准EI源,离子源温度230 ℃;电子倍增管电压2 447.06 V;质量扫描范围m/z为50~650,升温程序见表1。

1.5.3 采用HPLC法测定3种工艺鲜竹沥饮片中苯酚及愈创木酚的含量

针对GC-MS的分析结果以及急性毒性实验中干馏制鲜竹沥饮片对胃肠道的不良影响,结合对差异成分毒理学参数的查询,推测酚类物质苯酚和愈创木酚可能是引起胃肠道刺激的主要因素,为验证该推测,进一步采用文献[19]已报道的HPLC方法,对3种工艺制备的鲜竹沥饮片中苯酚及愈创木酚的含量进行定量分析。

1.6 急性毒性实验

鲜竹沥尚无文献记载其具有毒性,因此急性毒性实验选用最大给药量试验方法。KM小鼠80只,体质量(20±2)g,雌雄各半,随机分为4组,每组20只。分别为正常对照组(normal control,NC)、火烤工艺组(fire roasting process,FR)、回流提取工艺组(reflux extraction process,RE)、干馏工艺组(dry distillation process,DD)。样品经真空冷冻冻干后,复溶,配制成适宜灌胃的浓度,以小鼠经口给药容量最大值40 mL·kg^-1^[20]给药,24 h内灌胃给药3次,每间隔8 h给药一次。最终给药剂量分别为:FR组为5 860 mL·kg·d^-1,RE组为12 610 mL·kg·d^-1,DD组为2 113 mL·kg·d^-1(依据市售鲜竹沥口服液临床成人每日口服剂量为60 mL·60 kg^-1计算,分别等效于临床剂量的650、1 400、235倍)。如前所述,给药后连续14 d观察小鼠体重变化、饮食、外观、行为、分泌物、排泄物、死亡情况等^[21],对濒死及死亡动物应及时进行大体解剖,依据观察结果,在观察期结束后再选择是否留观或结束试验,必要时,对可疑病变器官进行组织病理学检查。

1.7 亚急性毒性实验

与传统火烤工艺以及回流提取工艺相比,干馏制鲜竹沥饮片在物质种类及含量方面均显著升高。且急性毒性实验提示,干馏制鲜竹沥饮片对小鼠体重增长以及胃肠道组织形态存在显著性影响,因此锁定干馏制鲜竹沥开展进一步的亚急性毒性测试。SD大鼠80只,体质量(200±20)g,雌雄各半,随机分为4组,每组20只。分别为正常对照组(NC)、干馏低剂量组(low-dry distillation process,DL,10 mL·kg^-1)、干馏中剂量组(medium-dry distillation process,DM,40 mL·kg^-1)和干馏高剂量组(high-dry distillation process,DH,70 mL·kg^-1),剂量设置依据:依据市售鲜竹沥口服液临床成人每日口服量为每60 kg60 mL计算,分别等效于临床剂量的30、120、210倍;因半数致死量(LD₅₀)求不出,试验剂量应尽可能涵盖预期摄入量的100倍剂量,因此将中剂量组设置为120倍。每天灌胃给药1次,连续给药30 d,给药剂量设置为5 mL·kg^-1,正常对照组按体质量给予等量纯净水。第1次给药前及每周动物称重,每天观察记录各组大鼠的一般状态、中毒及死亡情况,并记录其摄食量。末次给药后禁食不禁水12 h,记录体质量,异氟烷麻醉处死,腹主动脉采血收集血液,进行血常规、血生化测定^[22];解剖动物,取材并对主要脏器进行称重,并计算脏器系数;将心、肝、脾、肺、肾、睾丸/卵巢、胃、肠道等器官组织置体积分数4%甲醛溶液固定后,石蜡包埋,苏木精-伊红(HE)染色后在光学显微镜下观察病理变化^[23]。

1.8 统计学分析

本研究中急性毒性实验采用Bliss法计算不同给药组小鼠的LD₅₀,将各组得到的数据录入Graphpad Prism6软件,经计算得到LD₅₀及95%可信限区间。

采用SAS 8.2统计软件进行数据处理与分析,数据表示为平均值±标准差(

$\stackrel{-}{x}$

±s)。各组间数据进行比较之前先进行正态性和方差齐性检验,采用单因素方差(one-way ANOVA)分析数据,多组间两两比较采用LSD-t检验,P<0.05为差异有统计学意义。

2 结果

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2.1 不同工艺鲜竹沥饮片物质成分分析

2.1.1 GC-MS方法测定的3种工艺鲜竹沥饮片物质成分的对比分析

不同工艺鲜竹沥化学成分种类和含量差异较大,从不同工艺鲜竹沥成分中共鉴定出54种,包括酚类16种、酮类9种、酯类11种、醛类7种、羧酸类3种、醇类1种,其他7种(表2~3)。另外采用PCA和OPLS-DA法,得出变量权重值(VIP)>1,且t检验有统计学意义差异性成分中,其中回流提取法与火烤法的差异性成分有5个,分别是愈创木酚、糠醛、糠醇、2,3-二氢苯并呋喃、油酸酰胺;火烤法和干馏法的差异性成分有14个,分别为苯酚、4-乙基愈创木酚、紫丁香醇、(E)-2-甲氧基-4-(1-丙烯基苯酚)、2,4-二叔丁基苯酚、4-羟基丁酸乙酰酯、乙酸糠酯、1-羟基-2-丁酮、1-乙酰氧基-2-丁酮、麦芽醇、糠醛、糠醇、异丁酸酐、2,3-二氢苯并呋喃;回流提取法和干馏法的差异性成分有11个,分别为苯酚、愈创木酚、紫丁香醇、4-羟基丁酸乙酰酯、gamma-丁内酯、乙酸糠酯、糠醛、糠醇、异丁酸酐、2,3-二氢苯并呋喃、油酸酰胺。另外,结合原始数据分析发现乙酸糠酯、异丁酸酐、苯酚、糠醇是区别干馏法和其他2种工艺的差异性成分,其中,乙酸糠酯、异丁酸酐还是干馏法特有的特征性成分;糠醛、2,3-二氢苯并呋喃、糠醇是区别火烤法与其他2种工艺的差异性成分;愈创木酚、糠醛、2,3-二氢苯并呋喃、油酸酰胺、糠醇是区别回流提取法与其他工艺差异性成分(表4)。由此可见,本实验通过主成分分析(PCA)及正交偏最小二乘法判别分析(OPLS-DA)方法对鲜竹沥进行工艺差异性分析与比较,据此可鉴别不同工艺鲜竹沥。值得关注的是,苯酚和愈创木酚对黏膜存在刺激,一定剂量下出现可观测到的不良反应。该成分分析结果也提示物质基础的巨大变化可能会存在潜在的安全性风险。

2.1.2 3种工艺鲜竹沥饮片中苯酚及愈创木酚含量测定结果

HPLC分析结果表明,火烤和回流提取工艺中均未检测到愈创木酚,这与GC-MS的结果不完全一致,如回流提取工艺的GC-MS分析结果中也未检测到愈创木酚,火烤工艺检测到苯酚和愈创木酚,但相对含量与干馏工艺比较均存有较大差异。干馏制鲜竹沥饮片中检测到苯酚和愈创木酚的含量分别是(0.097±0.004)和(0.150±0.017)mg·mL^-1(表5)。

2.2 急性毒性试验

给药后所有小鼠均未出现死亡,未能测出LD₅₀。在观察期内,干馏工艺组小鼠较其他组精神倦怠、活动减弱、呼吸有喘鸣音,大便偶为稀便状。干馏工艺组小鼠体质量增长缓慢,给药一周后小鼠体质量与正常对照组相比存在显著性差异(表6)。其他各组小鼠一般情况良好,摄食量、饮水量基本正常,毛色光滑,呼吸正常,大小便正常,未见异常行为活动。观察结束后大体解剖结果显示,干馏工艺组胃、肠呈现泡样、充气状(图1),但病理报告分析显示未见明显异常,留观该组动物雌雄各5只,胃肠组织肉眼观察在10~12 d恢复正常。

2.3 亚急性毒性试验结果

2.3.1 对大鼠一般状况、体质量及脏器系数的影响

给药期间,高剂量组大鼠较其他组活动减弱、精神倦怠,对刺激反应不敏感,大便渐为稀便状,大鼠后期饮食饮水量稍有下降,但与其他各组比较,差异无统计学意义。其他各组大鼠一般情况良好,毛色光滑,呼吸正常,摄食饮水和排泄粪便均基本正常,未见异常行为。大鼠灌胃给药后,每天称重1次,各给药组与正常对照组相比较体质量增长差异无统计学意义,结果见表7。对所取脏器进行称重,计算其脏器系数(公式1)^[24]。

公式(1)脏器系数(%)=脏器质量(g)/体质量(g)×100%

与正常对照组相比,低、中剂量组的各项脏器指数无明显改变;干馏高剂量组的心、肝、肺和肾指数与正常对照组相比均增大(P<0.05),结果见表8。

2.3.2 对血常规指标的影响

与正常对照组相比,各给药组大鼠的白细胞数目(WBC)、中性粒细胞百分比(NEUT)、淋巴细胞百分比(LYMPH)、嗜碱性粒细胞百分比(BASO)、平均红细胞血红蛋白含量(MCH)、平均红细胞血红蛋白浓度(HGB)、血小板数目(PLT)水平均无显著性差异;中剂量组的嗜酸性粒细胞(EO)百分比显著提高(P<0.01);高剂量组的红细胞数目(RBC)、血红蛋白浓度及平均血小板体积(MPV)有显著升高(P<0.05),结果见表9。

2.3.3 对血生化指标的影响

与正常对照组相比,各给药组的葡萄糖(Glu)、丙氨酸氨基转移酶(ALT)、白蛋白(ALB)、甘油三酯(TG)、总胆固醇(TC)、肌酐(CREA)、尿素(UREA)水平均无显著性差异;高剂量组大鼠血浆中总蛋白(TP)水平显著升高(P<0.05),结果见表10。

2.3.4 对主要脏器组织病理变化的影响

病理分析报告显示,与正常对照组相比,各给药组主要脏器(心脏、肝脏、脾脏、肺脏、肾脏、睾丸/卵巢)均未见明显病理改变(图2)。各给药组胃肠组织呈现轻度至中度病理改变,见图3、4。具体表现如下:与正常对照组相比,低、中、高剂量组胃组织结构轻度异常,偶见黏膜层有少量炎症细胞浸润;中、高剂量组有少量胃上皮化生、萎缩变性;高剂量组可见少量胃上皮细胞紊乱脱落。

与正常对照组比较,低剂量组偶见(2/8)炎症细胞浸润;中、高剂量组肠组织结构中度异常(3/8和6/8),表现为部分区域杯状细胞数量可见减少,可见有明显的炎症细胞浸润;中剂量组偶见肠黏膜层有少量红细胞;高剂量组可见上皮细胞排列紊乱,变性坏死。

3 讨论

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物质基础决定效应结局(毒效或药效)。研究结果表明,3种工艺制备的鲜竹沥饮片物质基础发生了较大的变化,特别是在干馏工艺中一些酚类成分在种类和含量方面存在明显差别,例如愈创木酚(0.150±0.017)mg·mL^-1、苯酚(0.097±0.004)mg·mL^-1等^[25-26],而这些酚类成分本身对黏膜存在较强的刺激性^[27-29]。这合理地解释了在急性毒性试验和亚急性毒性试验中,干馏制鲜竹沥饮片对胃肠道组织结构及功能有较为明显的影响。与此同时,我们也注意到,愈创木酚和苯酚在HPLC的分析结果与GC-MS结果不完全一致,究其原因主要是GC-MS采用峰面积归一化法计算相对含量,而HPLC采用标准品峰面积比对计算含量。测量及计算方法的差异,造成两者结果并不完全一致。

急性毒性试验和亚急性毒性试验中样品的剂量问题也值得被关注。在实验设计中,为了与市售鲜竹沥饮片的给药剂量单位保持一致,各工艺组样品的剂量单位均设置为mL·kg^-1。如文中所述,火烤工艺组为5 860 mL·kg^-1、回流提取工艺组为12 610 mL·kg^-1、干馏工艺组2 113 mL·kg^-1。这些组别的剂量数值悬殊且无法反映真实的给药情况,根本原因是制备工艺差异导致的饮片得率不一致。但应当要注意到的是,即使是换算为竹子的生药量,3种工艺的剂量值仍不具备可比性。且市售鲜竹沥饮片的制备工艺参数及过程不可考,不同工艺制备的鲜竹沥饮片质量评价难以统一尺度。2022年7月,江西省药品监督管理局发布了鲜竹沥中药饮片标准炮制项下将火制法和干馏法工艺纳入,舍弃了回流提取法。虽然这在一定程度上规范了鲜竹沥饮片的质量标准及工艺参数,但火烤法和干馏法仍然在物质基础上存在显著差异^[30],将两者统一到相同质量尺度下仍不能规避物质基础差异导致的效应结局(毒效或药效)不一致的风险。本文通过对不同工艺鲜竹沥饮片的物质成分进行分析,进一步从急性毒性和亚急性毒性角度分析干馏制鲜竹沥饮片的毒性潜能,为后续市场上鲜竹沥饮片的质量控制提出科学依据,基于本文的研究结果,认为新颁布的质量标准仍存在可优化的空间,建议基于效应结局对不同工艺鲜竹沥饮片的优效性进行评价,并依据优效性评价结果进一步规范生产工艺和优化质量标准,这是本文的主要科学价值。

随着国家“双碳”目标的逐步推进,干馏制鲜竹沥因其在节能、降耗、增效方面的优势,正逐步取代原有的传统工艺。基于本文的研究结果,可为干馏制鲜竹沥饮片的临床安全应用提供指导。虽然在急性毒性试验和亚急性毒性试验高剂量组中均观察到干馏制鲜竹沥饮片对小鼠的胃肠道存在一定不良影响,然而亚急性毒性试验所用剂量涵盖了成人临床等效剂量的100倍,且未出现明显的不良效应。基于本研究结果的合理推论可表明不同工艺的鲜竹沥饮片总体安全性较好。

基金

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江西省中医药管理局科技计划项目资助(2022B1022)
江西中医药大学博士科研启动金项目资助(2021BSZR018)
江西中医药大学青年教师培养重点学科课题资助(2021jzzdxk001)
江西省自然科学基金项目资助(20224BAB216103)

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2024年第59卷第6期

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文章信息

doi: 10.11669/cpj.2024.06.005

接收时间：2023-08-10
首发时间：2026-04-08
出版时间：2024-03-22

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作者

出版历史

收稿日期：2023-08-10

基金

江西省中医药管理局科技计划项目资助(2022B1022)

江西中医药大学博士科研启动金项目资助(2021BSZR018)

江西中医药大学青年教师培养重点学科课题资助(2021jzzdxk001)

江西省自然科学基金项目资助(20224BAB216103)

作者信息

¹ 江西中医药大学现代中药制剂教育部重点实验室, 南昌 330004

² 江西中医药大学经典名方现代中药创制全国重点实验室, 南昌 330004

³ 江西中医药大学附属医院, 南昌 330004

通讯作者:

^*徐焕华,男,副教授研究方向:中药药理与毒理 Tel:(0791)87119032;杨明,男,教授研究方向:中药炮制及药剂研究 Tel:(0791)87119118

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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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RefWorks
TxT

Heating rate/℃·min^-1	T/℃	t/min
0	30	5
3	40	4
5	60	2
10	80	2
10	110	3
5	120	2
5	144	0
3	180	0
8	280	1
5	300	0

Heating rate/℃·min^-1

T/℃

t/min

110

120

144

180

280

300

No.	t_R	Library /ID	CAS	Match	Relative Content/%
1	19.98	Phenol	108-95-2	95	1.47	0.23	2.95
2	23.21	2-methyl-Phenol	95-48-7	98	-	-	0.45
3	24.10	p-Cresol	106-44-5	92	0.38	-	0.40
4	24.55	2-methoxy-guaiacol	90-05-1	96	1.68	-	5.98
5	27.72	4-ethyl-phenol	123-07-9	95	1.84	-	1.16
6	28.61	Creosol	93-51-6	89	-	-	0.89
7	28.65	6-methoxy-m-cresol	1195-09-1	83	1.02	-	-
8	32.12	4-ethyl-2-methoxy-phenol	2785-89-9	91	-	-	1.59
9	33.53	4-hydroxy-3-methoxystyrene	7786-61-0	93	1.44	-	1.46
10	35.22	2,6-dimethoxy-syringol	91-10-1	97	2.22	-	6.96
11	35.50	Eugenol	97-53-0	95	-	-	0.25
12	35.91	2-methoxy-4-propyl-dihydroeugenol	2785-87-7	96	-	-	0.16
13	39.00	trans-Isoeugenol	5932-68-3	98	-	-	1.55
14	41.21	2,4-di-t-butylphenol	96-76-4	91	1.53	1.83	0.32
15	44.30	2,6-dimethoxy-4-allylphenol	6627-88-9	89	0.19	-	0.54
16	61.94	2,2'-methylenebis(6-tert-butyl-4-methylphenol)	119-47-1	96	0.16	1.59	0.11
17	12.66	5-methyl-alpha-angelica lactone	591-12-8	80	-	-	0.14
18	13.22	diacetate glycol diacetate	111-55-7	88	1.77	-	1.73
19	15.68	4-hydroxy-butanoic acid	591-81-1	83	0.81	-	2.03
20	15.47	Butyrolactone	96-48-0	87	1.32	-	2.14
21	15.78	Methyl acetoxyacetate	5837-80-9	85	-	-	0.35
22	19.48	Methyl 2-furoate	611-13-2	90	-	-	0.49
23	20.20	Methyl 4-oxopentanoate	624-45-3	87	-	-	0.42
24	20.46	Furan-2-ylmethyl acetate	623-17-6	97	-	-	2.20
25	42.19	Methyl Laurate	111-82-0	96	-	2.63	-
26	54.70	Methyl palmitate	112-39-0	97	-	4.08	-
27	58.15	Methyl stearate	112-61-8	99	-	2.53	-
28	4.62	Acetoin	513-86-0	86	-	-	0.22
29	6.73	1-Hydroxy-2-butanone	5077-67-8	82	-	-	1.68
30	6.85	Carbamic acid,	79069-13-9	92	0.82	-	0.77
31	7.76	Cyclopentanone	120-92-3	86	-	-	0.11
32	8.61	2-methyl-tetrahydrofuran-3-one	3188-00-9	90	-	-	0.57
33	13.19	2-Propanone, 1-(acetyloxy)-1-acetoxyacetone	592-20-1	81	4.89	-	-
34	13.82	2-cyclopentene-1, 4-dione	930-60-9	86	-	-	0.21
35	19.16	1-acetory-2-butanone	1575-57-1	90	-	-	1.08
36	25.57	Maltol	118-71-8	98	-	-	1.07
37	10.05	Furfural	98-01-1	95	14.27	-	16.26
38	18.67	5-methyl-2-furaldehyde	620-02-0	97	0.74	-	1.64
39	20.99	2 Formyl-1H-pyrrole	1003-29-8	87	-	-	0.20
40	35.64	4-hydroxy-benzaldehyde	123-08-0	92	-	1.11	0.85
41	37.14	Vanillin	121-33-5	90	-	-	0.17
42	46.24	4-hydroxy-3,5-dimethoxy-syringaldehyde	134-96-3	96	-	-	0.05
43	48.67	3-(4-hydroxy-3-methoxyphenyl)-coniferyl aldehyde	458-36-6	93	-	-	0.09
44	4.34	Propanoic acid	79-09-4	81	-	-	0.26
45	7.91	Butanoic acid	107-92-6	87	-	-	0.06
46	41.81	Homovanillic acid	306-08-1	87	-	-	0.22
47	11.81	2-Furanmethanol	98-00-0	98	9.25	0.27	7.69
48	9.41	methylpyrazine	109-08-0	90	-	-	0.31
49	10.45	hexamethyl-Cyclotrisiloxane	541-05-9	90	-	5.07	-
50	20.86	Isobutyric acid anhydride	97-72-3	84	-	-	3.17
51	21.39	octamethyl-Cyclotetrasiloxane	556-67-2	91	-	2.75	-
52	29.62	2,3-dihydro-coumaran	496-16-2	94	8.46	-	4.11
53	41.45	tetradecamethyl-Cycloheptasiloxane	107-50-6	93	-	5.39	-
54	61.20	(Z)-oleamide	301-02-0	96	0.38	5.72	0.80

No.

t_R

Library
/ID

CAS

Match

Relative Content/%

19.98

Phenol

108-95-2

1.47

0.23

2.95

23.21

2-methyl-Phenol

95-48-7

0.45

24.10

p-Cresol

106-44-5

0.38

0.40

24.55

2-methoxy-guaiacol

90-05-1

1.68

5.98

27.72

4-ethyl-phenol

123-07-9

1.84

1.16

28.61

Creosol

93-51-6

0.89

28.65

6-methoxy-m-cresol

1195-09-1

1.02

32.12

4-ethyl-2-methoxy-phenol

2785-89-9

1.59

33.53

4-hydroxy-3-methoxystyrene

7786-61-0

1.44

1.46

35.22

2,6-dimethoxy-syringol

91-10-1

2.22

6.96

35.50

Eugenol

97-53-0

0.25

35.91

2-methoxy-4-propyl-dihydroeugenol

2785-87-7

0.16

39.00

trans-Isoeugenol

5932-68-3

1.55

41.21

2,4-di-t-butylphenol

96-76-4

1.53

1.83

0.32

44.30

2,6-dimethoxy-4-allylphenol

6627-88-9

0.19

0.54

61.94

2,2'-methylenebis(6-tert-butyl-4-methylphenol)

119-47-1

0.16

1.59

0.11

12.66

5-methyl-alpha-angelica lactone

591-12-8

0.14

13.22

diacetate glycol diacetate

111-55-7

1.77

1.73

15.68

4-hydroxy-butanoic acid

591-81-1

0.81

2.03

15.47

Butyrolactone

96-48-0

1.32

2.14

15.78

Methyl acetoxyacetate

5837-80-9

0.35

19.48

Methyl 2-furoate

611-13-2

0.49

20.20

Methyl 4-oxopentanoate

624-45-3

0.42

20.46

Furan-2-ylmethyl acetate

623-17-6

2.20

42.19

Methyl Laurate

111-82-0

2.63

54.70

Methyl palmitate

112-39-0

4.08

58.15

Methyl stearate

112-61-8

2.53

4.62

Acetoin

513-86-0

0.22

6.73

1-Hydroxy-2-butanone

5077-67-8

1.68

6.85

Carbamic acid,

79069-13-9

0.82

0.77

7.76

Cyclopentanone

120-92-3

0.11

8.61

2-methyl-tetrahydrofuran-3-one

3188-00-9

0.57

13.19

2-Propanone, 1-(acetyloxy)-1-acetoxyacetone

592-20-1

4.89

13.82

2-cyclopentene-1, 4-dione

930-60-9

0.21

19.16

1-acetory-2-butanone

1575-57-1

1.08

25.57

Maltol

118-71-8

1.07

10.05

Furfural

98-01-1

14.27

16.26

18.67

5-methyl-2-furaldehyde

620-02-0

0.74

1.64

20.99

2 Formyl-1H-pyrrole

1003-29-8

0.20

35.64

4-hydroxy-benzaldehyde

123-08-0

1.11

0.85

37.14

Vanillin

121-33-5

0.17

46.24

4-hydroxy-3,5-dimethoxy-syringaldehyde

134-96-3

0.05

48.67

3-(4-hydroxy-3-methoxyphenyl)-coniferyl aldehyde

458-36-6

0.09

4.34

Propanoic acid

79-09-4

0.26

7.91

Butanoic acid

107-92-6

0.06

41.81

Homovanillic acid

306-08-1

0.22

11.81

2-Furanmethanol

98-00-0

9.25

0.27

7.69

9.41

methylpyrazine

109-08-0

0.31

10.45

hexamethyl-Cyclotrisiloxane

541-05-9

5.07

20.86

Isobutyric acid anhydride

97-72-3

3.17

21.39

octamethyl-Cyclotetrasiloxane

556-67-2

2.75

29.62

2,3-dihydro-coumaran

496-16-2

8.46

4.11

41.45

tetradecamethyl-Cycloheptasiloxane

107-50-6

5.39

61.20

(Z)-oleamide

301-02-0

0.38

5.72

0.80

Library /ID	FR vs DD	FR vs RE	RE vs DD
Phenol	1.170	0.000	-	-	1.153	0.000
2-methoxy-Phenol	-	-	1.214	0.002	1.738	0.000
4-ethyl-2-methoxy-Phenol	1.319	0.004	-	-	-	-
2,6-dimethoxy-syringol	2.326	0.001	-	-	1.898	0.000
trans-Isoeugenol	1.344	0.002	-	-	-	-
2,4-di-t-butylphenol	1.108	0.000	-	-	-	-
4-hydroxy-butanoic acid	1.102	0.002	-	-	1.010	0.000
Butyrolactone	-	-	-	-	1.010	0.000
Furan-2-ylmethyl-acetate	1.598	0.002	-	-	1.051	0.002
1-Hydroxy-2-butanone	1.377	0.003	-	-	-	-
1-(acetyloxy)-2-Butanone	1.102	0.004	-	-	-	-
Maltol	1.051	0.005	-	-	-	-
Furfural	1.180	0.001	2.158	0.002	2.915	0.000
2-Furanmethanol	1.301	0.000	1.738	0.001	1.956	0.000
Isobutyric acid anhydride	1.895	0.003	-	-	1.246	0.003
2,3-dihydro-coumaran	2.188	0.001	1.640	0.002	1.450	0.000
(Z)-oleamide	-	-	1.284	0.001	1.563	0.011

Library
/ID

FR vs DD

FR vs RE

RE vs DD

VIP

Phenol

1.170

0.000

1.153

0.000

2-methoxy-Phenol

1.214

0.002

1.738

0.000

4-ethyl-2-methoxy-Phenol

1.319

0.004

2,6-dimethoxy-syringol

2.326

0.001

1.898

0.000

trans-Isoeugenol

1.344

0.002

2,4-di-t-butylphenol

1.108

0.000

4-hydroxy-butanoic acid

1.102

0.002

1.010

0.000

Butyrolactone

1.010

0.000

Furan-2-ylmethyl-acetate

1.598

0.002

1.051

0.002

1-Hydroxy-2-butanone

1.377

0.003

1-(acetyloxy)-2-Butanone

1.102

0.004

Maltol

1.051

0.005

Furfural

1.180

0.001

2.158

0.002

2.915

0.000

2-Furanmethanol

1.301

0.000

1.738

0.001

1.956

0.000

Isobutyric acid anhydride

1.895

0.003

1.246

0.003

2,3-dihydro-coumaran

2.188

0.001

1.640

0.002

1.450

0.000

(Z)-oleamide

1.284

0.001

1.563

0.011

Group	Library/ID
“DD vs FR”vs“DD vs RE”	2-Furanmethanol, acetate³⁾; Propanoic acid, 2-methyl-, anhydride³⁾; Phenol¹⁾²⁾³⁾; 2-Furanmethanol¹⁾²⁾³⁾
“FR vs RE”vs“FR vs DD”	Furfural¹⁾³⁾; 2,3-dihydro-¹⁾³⁾; 2-Furanmethanol¹⁾²⁾³
“RE vs FR”vs“RE vs DD”	Phenol, 2-methoxy-¹⁾³⁾; Furfural¹⁾³⁾; 2,3-dihydro-¹⁾³⁾; 9-Octadecenamide, (Z)-¹⁾²⁾³⁾; 2-Furanmethanol¹⁾²⁾³⁾
“RE”vs“FR”vs“DD”	2-Furanmethanol¹⁾²⁾³⁾; Furfural¹⁾³⁾; Benzofuran, 2,3-dihydro-¹⁾³⁾

Group

Library/ID

“DD vs FR”vs“DD vs RE”

2-Furanmethanol, acetate³⁾; Propanoic acid, 2-methyl-, anhydride³⁾; Phenol¹⁾²⁾³⁾; 2-Furanmethanol¹⁾²⁾³⁾

“FR vs RE”vs“FR vs DD”

Furfural¹⁾³⁾; 2,3-dihydro-¹⁾³⁾; 2-Furanmethanol¹⁾²⁾³

“RE vs FR”vs“RE vs DD”

Phenol, 2-methoxy-¹⁾³⁾; Furfural¹⁾³⁾; 2,3-dihydro-¹⁾³⁾; 9-Octadecenamide, (Z)-¹⁾²⁾³⁾; 2-Furanmethanol¹⁾²⁾³⁾

“RE”vs“FR”vs“DD”

2-Furanmethanol¹⁾²⁾³⁾; Furfural¹⁾³⁾; Benzofuran, 2,3-dihydro-¹⁾³⁾

Process	Phenol/mg·mL^-1	Phenol, 2-methoxyphenol/mg·mL^-1
FR	0.031±0.002	ND
RE	ND	ND
DD	0.097±0.004	0.150±0.017

Process

Phenol/mg·mL^-1

Phenol, 2-methoxyphenol/mg·mL^-1

0.031±0.002

0.097±0.004

0.150±0.017

Group	m(0 d)/g	m(7 d)/g	m(14 d)/g
NC(♂)	23.2±1.16	36.3±2.23	41.9±3.67
NC(♀)	23.1±0.92	30.3±2.61	36.7±4.01
FR(♂)	23.9±1.94	35.3±2.52	42.2±2.67
FR(♀)	22.8±1.51	30.4±2.33	34.9±3.17
RE(♂)	22.8±1.43	34.7±3.36	40.6±4.04
RE(♀)	23.5±1.22	29.7±2.33	35.3±5.21
DD(♂)	22.3±1.62	26.9±3.34¹⁾	29.1±5.86¹⁾
DD(♀)	23.1±0.88	24.3±2.49¹⁾	26.5±3.19¹⁾

Group

m(0 d)/g

m(7 d)/g

m(14 d)/g

NC(♂)

23.2±1.16

36.3±2.23

41.9±3.67

NC(♀)

23.1±0.92

30.3±2.61

36.7±4.01

FR(♂)

23.9±1.94

35.3±2.52

42.2±2.67

FR(♀)

22.8±1.51

30.4±2.33

34.9±3.17

RE(♂)

22.8±1.43

34.7±3.36

40.6±4.04

RE(♀)

23.5±1.22

29.7±2.33

35.3±5.21

DD(♂)

22.3±1.62

26.9±3.34¹⁾

29.1±5.86¹⁾

DD(♀)

23.1±0.88

24.3±2.49¹⁾

26.5±3.19¹⁾

Group	m(0 d)/g	m(7 d)/g	m(14 d)/g	m(21 d)/g	m(28 d)/g
NC(♂)	285.4	±8.89	342.3	±11.71	364.7	±13.54	405.1	±18.12	429.8	±19.40
NC(♀)	267.3	±7.36	322.4	±12.34	332.8	±16.57	378.2	±19.33	385.3	±18.74
DL(♂)	285.8	±9.68	343.7	±14.37	371.5	±18.54	412.5	±24.00	436.3	±27.79
DL(♀)	271.2	±8.22	318.3	±13.43	339.8	±16.41	364.5	±21.13	390.2	±20.63
DM(♂)	285.6	±9.00	335.2	±29.95	350.1	±39.59	387.8	±43.78	403.2	±53.39
DM(♀)	271.5	±10.23	324.3	±17.46	329.5	±12.95	354.9	±27.80	381.2	±32.21
DH(♂)	285.5	±6.04	334.9	±22.36	364.2	±31.24	397.9	±36.53	405.4	±37.66
DH(♀)	268.4	±7.38	318.3	±15.39	325.3	±12.95	360.1	±33.51	379.9	±42.81

Group

m(0 d)/g

m(7 d)/g

m(14 d)/g

m(21 d)/g

m(28 d)/g

NC(♂)

285.4

±8.89

342.3

±11.71

364.7

±13.54

405.1

±18.12

429.8

±19.40

NC(♀)

267.3

±7.36

322.4

±12.34

332.8

±16.57

378.2

±19.33

385.3

±18.74

DL(♂)

285.8

±9.68

343.7

±14.37

371.5

±18.54

412.5

±24.00

436.3

±27.79

DL(♀)

271.2

±8.22

318.3

±13.43

339.8

±16.41

364.5

±21.13

390.2

±20.63

DM(♂)

285.6

±9.00

335.2

±29.95

350.1

±39.59

387.8

±43.78

403.2

±53.39

DM(♀)

271.5

±10.23

324.3

±17.46

329.5

±12.95

354.9

±27.80

381.2

±32.21

DH(♂)

285.5

±6.04

334.9

±22.36

364.2

±31.24

397.9

±36.53

405.4

±37.66

DH(♀)

268.4

±7.38

318.3

±15.39

325.3

±12.95

360.1

±33.51

379.9

±42.81

Group	Heart index/%	Liver index/%	Spleen index/%	Lung index/%	Kidney index/%
NC(♂)	0.32	±0.02	2.65	±0.14	0.21	±0.01	0.36	±0.08	0.62	±0.15
NC(♀)	0.29	±0.03	2.42	±0.15	0.18	±0.01	0.33	±0.06	0.52	±0.21
DL(♂)	0.30	±0.01	2.58	±0.14	0.22	±0.04	0.32	±0.06	0.64	±0.03
DL(♀)	0.28	±0.02	2.47	±0.18	0.17	±0.03	0.30	±0.05	0.53	±0.19
DM(♂)	0.31	±0.02	2.62	±0.23	0.22	±0.05	0.36	±0.05	0.69	±0.03
DM(♀)	0.29	±0.01	2.51	±0.17	0.18	±0.04	0.34	±0.08	0.61	±0.04
DH(♂)	0.36	±0.04¹⁾	3.19	±0.45¹⁾	0.22	±0.01	0.44	±0.06¹⁾	0.75	±0.06¹⁾
DH(♀)	0.33	±0.05¹⁾	2.91	±0.33¹⁾	0.19	±0.03	0.41	±0.07¹⁾	0.70	±0.04¹⁾

Group

Heart index/%

Liver index/%

Spleen index/%

Lung index/%

Kidney index/%

NC(♂)

0.32

±0.02

2.65

±0.14

0.21

±0.01

0.36

±0.08

0.62

±0.15

NC(♀)

0.29

±0.03

2.42

±0.15

0.18

±0.01

0.33

±0.06

0.52

±0.21

DL(♂)

0.30

±0.01

2.58

±0.14

0.22

±0.04

0.32

±0.06

0.64

±0.03

DL(♀)

0.28

±0.02

2.47

±0.18

0.17

±0.03

0.30

±0.05

0.53

±0.19

DM(♂)

0.31

±0.02

2.62

±0.23

0.22

±0.05

0.36

±0.05

0.69

±0.03

DM(♀)

0.29

±0.01

2.51

±0.17

0.18

±0.04

0.34

±0.08

0.61

±0.04

DH(♂)

0.36

±0.04¹⁾

3.19

±0.45¹⁾

0.22

±0.01

0.44

±0.06¹⁾

0.75

±0.06¹⁾

DH(♀)

0.33

±0.05¹⁾

2.91

±0.33¹⁾

0.19

±0.03

0.41

±0.07¹⁾

0.70

±0.04¹⁾

Group	WBC/×10⁹·L^-1	RBC/×10¹²·L^-1	HGB/g·L^-1	PLT/×10⁹·L^-1	MCH/×10^-6 μg	MPV/×10^-15 L	EO/%
NC(♂+♀)	6.72±0.92	7.66±0.39	148.57±6.34	943.14±115.37	19.4±0.46	6.79±0.17	1.01±0.27
DL(♂+♀)	7.40±1.25	7.85±0.40	152.25±6.31	1022.13±113.15	19.44±0.71	6.91±0.18	1.81±1.03
DM(♂+♀)	6.77±1.81	8.19±0.40	155.86±5.69	965.57±259.54	19.03±0.72	7.07±0.26	2.93±2.71¹⁾
DH(♂+♀)	7.43±4.31	8.71±0.90¹⁾	166.17±16.91¹⁾	1 001.67±258.88	19.10±0.47	7.12±0.18¹⁾	0.88±0.54

Group

WBC/×10⁹·L^-1

RBC/×10¹²·L^-1

HGB/g·L^-1

PLT/×10⁹·L^-1

MCH/×10^-6 μg

MPV/×10^-15 L

EO/%

NC(♂+♀)

6.72±0.92

7.66±0.39

148.57±6.34

943.14±115.37

19.4±0.46

6.79±0.17

1.01±0.27

DL(♂+♀)

7.40±1.25

7.85±0.40

152.25±6.31

1022.13±113.15

19.44±0.71

6.91±0.18

1.81±1.03

DM(♂+♀)

6.77±1.81

8.19±0.40

155.86±5.69

965.57±259.54

19.03±0.72

7.07±0.26

2.93±2.71¹⁾

DH(♂+♀)

7.43±4.31

8.71±0.90¹⁾

166.17±16.91¹⁾

1 001.67±258.88

19.10±0.47

7.12±0.18¹⁾

0.88±0.54

Group	Glu /mmol·L^-1	ALT /U·L^-1	AST /U·L^-1	TP /g·L^-1	ALB /g·L^-1	TG /mmol·L^-1	TC /mmol·L^-1	CREA /μmol·L^-1	UREA /mmol·L^-1
NC(♂+♀)	4.92	±0.88	44.68	±7.29	108.58	±15.11	65.54	±2.13	32.9	±0.71	0.81	±0.32	1.81	±0.30	29.98	±2.51	6.61	±0.55
DL(♂+♀)	4.55	±0.95	34.64	±21.35	117.84	±18.33	62.31	±2.53	30.92	±1.50	0.60	±0.31	1.72	±0.27	23.16	±16.54	5.44	±3.01
DM(♂+♀)	4.82	±0.82	58.12	±25.47	140.96	±37.08	65.18	±1.68	32.18	±0.69	0.79	±0.36	1.74	±0.22	30.82	±8.14	6.37	±0.64
DH(♂+♀)	7.55	±7.68	52.84	±14.76	120.94	±43.56	73.82	±9.00¹⁾	29.5	±16.60	0.55	±0.20	1.55	±0.90	25.74	±3.48	6.01	±1.70

Group

Glu
/mmol·L^-1

ALT
/U·L^-1

AST
/U·L^-1

TP
/g·L^-1

ALB
/g·L^-1

TG
/mmol·L^-1

TC
/mmol·L^-1

CREA
/μmol·L^-1

UREA
/mmol·L^-1

NC(♂+♀)

4.92

±0.88

44.68

±7.29

108.58

±15.11

65.54

±2.13

32.9

±0.71

0.81

±0.32

1.81

±0.30

29.98

±2.51

6.61

±0.55

DL(♂+♀)

4.55

±0.95

34.64

±21.35

117.84

±18.33

62.31

±2.53

30.92

±1.50

0.60

±0.31

1.72

±0.27

23.16

±16.54

5.44

±3.01

DM(♂+♀)

4.82

±0.82

58.12

±25.47

140.96

±37.08

65.18

±1.68

32.18

±0.69

0.79

±0.36

1.74

±0.22

30.82

±8.14

6.37

±0.64

DH(♂+♀)

7.55

±7.68

52.84

±14.76

120.94

±43.56

73.82

±9.00¹⁾

29.5

±16.60

0.55

±0.20

1.55

±0.90

25.74

±3.48

6.01

±1.70