药学学报

No.	Metabolite	Model vs control		ACT vs model
1	Docosahexaenoic acid	-0.51	↓^c		1.11	↑^c
2	Osbond acid	0.65	↑^c	-0.086	↓^b
3	Cholesterol sulfate	-0.41	↓^c	0.80	↑^a
4	3-Indoxyl sulphate	0.52	↑^c	-0.009 3	↓^b
5	Deoxycholic acid	-0.75	↓^b	0.66	↑^b
6	L-α-Lysophosphatidylcholine	0.25	↑^c	-	-
7	16-Hydroxyhexadecanoic acid	0.94	↑^b	-	-
8	Linoleic acid	-0.12	↓^b	-0.006 2	↓^a
9	Sulfoglycolithocholic acid	-0.088	↓^b	0.12	↑^c
10	Allantoin	1.12	↑^b	-0.26	↓^a
11	2-Pentadecanone	-0.54	↓^a	-	-
12	Isodesmosine	-1.62	↓^c	0.21	↑^c
13	D-Gluconic acid	0.51	↑^a	-0.021	↓^a
14	5-Methoxyindoleacetic acid	-0.011	↓^c	-	-
15	Palmitic acid	0.64	↑^a	-	-
16	Arachidic acid	0.065	↑^b	-	-
17	Ferulic acid 4-sulfate	-2.50	↓^b	0.25	↑^b
18	D-Tryptophan	2.59	↑^a	0.49	↑^a
19	N-Acetyl-9-O-acetylneuraminic acid	0.91	↑^c	-0.062	↓^c
20	Homovanillic acid	3.41	↑^c	-0.088	↓^c
21	2-Keto-glutaramic acid	-1.27	↓^b	-0.85	↓^b
22	IpA	-1.18	↓^c	-0.42	↓^c
23	N-Arachidonylglycine	-1.00	↓^b	-0.98	↓^b
24	Ethyl eicosapentaenoic acid	-	-	-0.076	↓^b
25	Malic acid	-	-	1.16	↑^a
26	D-(-)-Erythrose	-	-	-0.42	↓^b
27	Citric acid	-	-	0.080	↑^b
28	7-Ketodeoxycholic acid	-	-	-0.34	↓^a
29	N-Undecanoylglycine	-	-	-0.17	↓^a
30	Glycochenodeoxycholic acid	-	-	1.25	↑^b
31	Decylubiquinone	-	-	0.93	↑^c

No.

Metabolite

Model vs control

ACT vs model

Log₂FC

Change trend

Log₂FC

Change trend

Docosahexaenoic acid

-0.51

↓^c

1.11

↑^c

Osbond acid

0.65

↑^c

-0.086

↓^b

Cholesterol sulfate

-0.41

↓^c

0.80

↑^a

3-Indoxyl sulphate

0.52

↑^c

-0.009 3

↓^b

Deoxycholic acid

-0.75

↓^b

0.66

↑^b

L-α-Lysophosphatidylcholine

0.25

↑^c

16-Hydroxyhexadecanoic acid

0.94

↑^b

Linoleic acid

-0.12

↓^b

-0.006 2

↓^a

Sulfoglycolithocholic acid

-0.088

↓^b

0.12

↑^c

Allantoin

1.12

↑^b

-0.26

↓^a

2-Pentadecanone

-0.54

↓^a

Isodesmosine

-1.62

↓^c

0.21

↑^c

D-Gluconic acid

0.51

↑^a

-0.021

↓^a

5-Methoxyindoleacetic acid

-0.011

↓^c

Palmitic acid

0.64

↑^a

Arachidic acid

0.065

↑^b

Ferulic acid 4-sulfate

-2.50

↓^b

0.25

↑^b

D-Tryptophan

2.59

↑^a

0.49

↑^a

N-Acetyl-9-O-acetylneuraminic acid

0.91

↑^c

-0.062

↓^c

Homovanillic acid

3.41

↑^c

-0.088

↓^c

2-Keto-glutaramic acid

-1.27

↓^b

-0.85

↓^b

IpA

-1.18

↓^c

-0.42

↓^c

N-Arachidonylglycine

-1.00

↓^b

-0.98

↓^b

Ethyl eicosapentaenoic acid

-0.076

↓^b

Malic acid

1.16

↑^a

D-(-)-Erythrose

-0.42

↓^b

Citric acid

0.080

↑^b

7-Ketodeoxycholic acid

-0.34

↓^a

N-Undecanoylglycine

-0.17

↓^a

Glycochenodeoxycholic acid

1.25

↑^b

Decylubiquinone

0.93

↑^c

No.	Metabolite	Model vs control		ACT vs model
1	Docosahexaenoic acid	-0.51	↓^c		1.11	↑^c
2	Osbond acid	0.65	↑^c	-0.086	↓^b
3	Cholesterol sulfate	-0.41	↓^c	0.80	↑^a
4	3-Indoxyl sulphate	0.52	↑^c	-0.009 3	↓^b
5	Deoxycholic acid	-0.75	↓^b	0.66	↑^b
6	L-α-Lysophosphatidylcholine	0.25	↑^c	-	-
7	16-Hydroxyhexadecanoic acid	0.94	↑^b	-	-
8	Linoleic acid	-0.12	↓^b	-0.006 2	↓^a
9	Sulfoglycolithocholic acid	-0.088	↓^b	0.12	↑^c
10	Allantoin	1.12	↑^b	-0.26	↓^a
11	2-Pentadecanone	-0.54	↓^a	-	-
12	Isodesmosine	-1.62	↓^c	0.21	↑^c
13	D-Gluconic acid	0.51	↑^a	-0.021	↓^a
14	5-Methoxyindoleacetic acid	-0.011	↓^c	-	-
15	Palmitic acid	0.64	↑^a	-	-
16	Arachidic acid	0.065	↑^b	-	-
17	Ferulic acid 4-sulfate	-2.50	↓^b	0.25	↑^b
18	D-Tryptophan	2.59	↑^a	0.49	↑^a
19	N-Acetyl-9-O-acetylneuraminic acid	0.91	↑^c	-0.062	↓^c
20	Homovanillic acid	3.41	↑^c	-0.088	↓^c
21	2-Keto-glutaramic acid	-1.27	↓^b	-0.85	↓^b
22	IpA	-1.18	↓^c	-0.42	↓^c
23	N-Arachidonylglycine	-1.00	↓^b	-0.98	↓^b
24	Ethyl eicosapentaenoic acid	-	-	-0.076	↓^b
25	Malic acid	-	-	1.16	↑^a
26	D-(-)-Erythrose	-	-	-0.42	↓^b
27	Citric acid	-	-	0.080	↑^b
28	7-Ketodeoxycholic acid	-	-	-0.34	↓^a
29	N-Undecanoylglycine	-	-	-0.17	↓^a
30	Glycochenodeoxycholic acid	-	-	1.25	↑^b
31	Decylubiquinone	-	-	0.93	↑^c

No.

Metabolite

Model vs control

ACT vs model

Log₂FC

Change trend

Log₂FC

Change trend

Docosahexaenoic acid

-0.51

↓^c

1.11

↑^c

Osbond acid

0.65

↑^c

-0.086

↓^b

Cholesterol sulfate

-0.41

↓^c

0.80

↑^a

3-Indoxyl sulphate

0.52

↑^c

-0.009 3

↓^b

Deoxycholic acid

-0.75

↓^b

0.66

↑^b

L-α-Lysophosphatidylcholine

0.25

↑^c

16-Hydroxyhexadecanoic acid

0.94

↑^b

Linoleic acid

-0.12

↓^b

-0.006 2

↓^a

Sulfoglycolithocholic acid

-0.088

↓^b

0.12

↑^c

Allantoin

1.12

↑^b

-0.26

↓^a

2-Pentadecanone

-0.54

↓^a

Isodesmosine

-1.62

↓^c

0.21

↑^c

D-Gluconic acid

0.51

↑^a

-0.021

↓^a

5-Methoxyindoleacetic acid

-0.011

↓^c

Palmitic acid

0.64

↑^a

Arachidic acid

0.065

↑^b

Ferulic acid 4-sulfate

-2.50

↓^b

0.25

↑^b

D-Tryptophan

2.59

↑^a

0.49

↑^a

N-Acetyl-9-O-acetylneuraminic acid

0.91

↑^c

-0.062

↓^c

Homovanillic acid

3.41

↑^c

-0.088

↓^c

2-Keto-glutaramic acid

-1.27

↓^b

-0.85

↓^b

IpA

-1.18

↓^c

-0.42

↓^c

N-Arachidonylglycine

-1.00

↓^b

-0.98

↓^b

Ethyl eicosapentaenoic acid

-0.076

↓^b

Malic acid

1.16

↑^a

D-(-)-Erythrose

-0.42

↓^b

Citric acid

0.080

↑^b

7-Ketodeoxycholic acid

-0.34

↓^a

N-Undecanoylglycine

-0.17

↓^a

Glycochenodeoxycholic acid

1.25

↑^b

Decylubiquinone

0.93

↑^c

No.	Lipid	Model vs control		ACT vs model		No.	Lipid	Model vs control		ACT vs model
1	PC(20:4/18:2)	0.69	↑^b		-0.66	↓^a		38	DG(18:1/22:5/0:0)	-0.57	↓^a	0.57	↑^a
2	TG(16:1/18:1/18:2)	-0.56	↓^a	0.60	↑^a	39	TG(16:0/20:0/22:4)	-0.51	↓^a	0.51	↑^a
3	PC(18:0/22:6)	0.64	↑^a	-	-	40	TG(18:0/18:2/20:4)	-0.50	↓^b	0.50	↑^a
4	TG(16:1/18:1/22:6)	-0.52	↓^a	0.63	↑^b	41	PI(16:0/22:4)	0.29	↑^a	-0.29	↓^a
5	TG(16:1/16:0/22:4)	-0.54	↓^a	0.56	↑^a	42	PI(18:0/22:6)	0.47	↑^a	-0.47	↓^a
6	PC(18:0/22:5)	1.61	↑^a	-1.85	↓^a	43	PC(20:0/20:2)	0.52	↑^a	-0.52	↓^a
7	CE(22:6)	1.16	↑^c	0.76	↑^a	44	CE(16:0)	0.52	↑^a	-0.52	↓^a
8	TG(16:1/18:1/22:2)	-0.78	↓^a	0.73	↑^a	45	PC(O-18:0/16:0)	0.53	↑^a	-0.53	↓^a
9	PC(20:4/20:4)	0.71	↑^b	-0.71	↓^a	46	PC(O-16:0/16:0)	0.54	↑^b	-0.54	↓^b
10	PC(14:0/22:5)	1.06	↑^c	-1.10	↓^b	47	PI(16:0/20:4)	0.55	↑^b	-0.55	↓^b
11	TG(18:1/22:6/22:6)	-0.78	↓^c	-	-	48	PC(P-18:1/20:5)	0.57	↑^b	-0.57	↓^b
12	TG(18:1/18:2/20:0)	-0.78	↓^a	-	-	49	PC(P-18:0/20:4)	0.58	↑^a	-0.58	↓^a
13	PC(18:0/22:4)	0.83	↑^b	-0.85	↓^b	50	PC(P-18:1/18:0)	0.59	↑^a	-0.59	↓^a
14	TG(15:0/18:1/20:3)	-0.87	↓^a	0.83	↑^a	51	PC(O-14:0/16:0)	0.63	↑^b	-0.63	↓^b
15	TG(15:0/16:0/20:4)	-0.90	↓^a	0.91	↑^a	52	PE(P-18:0/18:2)	0.64	↑^a	-0.64	↓^a
16	CE(22:4)	1.67	↑^b	1.07	↑^a	53	PC(16:0/18:0)	0.68	↑^a	-0.68	↓^a
17	PC(O-16:0/18:1)	0.73	↑^b	-0.76	↓^b	54	PC(22:1/20:3)	0.68	↑^b	-0.68	↓^b
18	TG(18:1/20:0/22:4)	-0.52	↓^a	-	-	55	PE(P-16:0/22:4)	0.68	↑^b	-0.69	↓^b
19	TG(15:0/18:1/22:5)	-0.78	↓^a	0.81	↑^a	56	PC(22:1/20:4)	0.69	↑^a	-0.70	↓^a
20	PC(20:5/22:5)	1.06	↑^a	-	-	57	PC(P-16:0/18:3)	0.83	↑^b	-0.83	↓^b
21	SM(d18:2/16:0)	0.82	↑^b	-0.79	↓^a	58	PE(P-16:0/22:6)	0.94	↑^b	-0.94	↓^b
22	CE(22:5)	1.41	↑^c	-0.77	↓^a	59	PI(16:0/16:1)	1.06	↑^a	-1.06	↓^a
23	PC(P-16:0/20:4)	0.64	↑^c	-0.56	↓^b	60	PC(16:1/14:0)	1.06	↑^a	-1.06	↓^a
24	PC(14:0/20:4)	1.11	↑^b	-1.16	↓^b	61	CE(18:3)	1.07	↑^b	-1.07	↓^b
25	PC(P-20:0/18:3)	0.62	↑^c	-	-	62	LysoPE(22:6/0:0)	1.07	↑^b	-1.07	↓^b
26	PC(18:0/18:0)	0.76	↑^a	-0.94	↓^a	63	PE(P-18:0/22:6)	1.08	↑^b	-1.08	↓^b
27	PC(P-18:0/20:5)	0.68	↑^b	-0.72	↓^b	64	GalCer(d18:1/22:0)	1.21	↑^b	-1.20	↓^b
28	TG(18:2/22:6/20:5)	-0.56	↓^b	-0.88	↓^b	65	GalCer(d18:1/24:1)	1.23	↑^b	-1.23	↓^b
29	PC(P-18:0/22:6)	0.67	↑^b	-0.72	↓^a	66	LysoPC(22:5)	1.31	↑^a	-1.31	↓^a
30	CE(20:5)	1.00	↑^c	0.95	↑^b	67	GalCer(d18:1/24:0)	1.33	↑^c	-1.33	↓^c
31	DG(18:2/22:6/0:0)	-0.95	↓^b	1.08	↑^c	68	GalCer(d18:1/23:0)	1.37	↑^b	-1.37	↓^b
32	Eicosadienoic acid	-0.72	↓^c	0.55	↑^b	69	TG(18:0/18:2/20:0)	-	-	-0.94	↓^a
33	Nonadeca-10-enoic acid	-0.58	↓^a	-	-	70	TG(14:0/20:5/22:5)	-	-	-0.62	↓^a
34	DG(18:1/20:5/0:0)	-0.68	↓^a	-0.62	↓^b	71	CE(20:3)	-	-	0.57	↑^b
35	DG(16:0/20:4/0:0)	-0.78	↓^a	0.78	↑^a	72	TG(16:1/20:5/22:6)	-	-	-0.83	↓^a
36	DG(18:2/20:5/0:0)	-0.67	↓^a	0.67	↑^a	73	CE(20:2)	-	-	0.73	↑^a
37	DG(18:2/22:5/0:0)	-0.61	↓^a	0.61	↑^a	74	α-Linolenic acid	-	-	-0.60	↓^a

No.

Lipid

Model vs control

ACT vs model

No.

Lipid

Model vs control

ACT vs model

Log₂FC

Change trend

Log₂FC

Change trend

Log₂FC

Change trend

Log₂FC

Change trend

PC(20:4/18:2)

0.69

↑^b

-0.66

↓^a

DG(18:1/22:5/0:0)

-0.57

↓^a

0.57

↑^a

TG(16:1/18:1/18:2)

-0.56

↓^a

0.60

↑^a

TG(16:0/20:0/22:4)

-0.51

↓^a

0.51

↑^a

PC(18:0/22:6)

0.64

↑^a

TG(18:0/18:2/20:4)

-0.50

↓^b

0.50

↑^a

TG(16:1/18:1/22:6)

-0.52

↓^a

0.63

↑^b

PI(16:0/22:4)

0.29

↑^a

-0.29

↓^a

TG(16:1/16:0/22:4)

-0.54

↓^a

0.56

↑^a

PI(18:0/22:6)

0.47

↑^a

-0.47

↓^a

PC(18:0/22:5)

1.61

↑^a

-1.85

↓^a

PC(20:0/20:2)

0.52

↑^a

-0.52

↓^a

CE(22:6)

1.16

↑^c

0.76

↑^a

CE(16:0)

0.52

↑^a

-0.52

↓^a

TG(16:1/18:1/22:2)

-0.78

↓^a

0.73

↑^a

PC(O-18:0/16:0)

0.53

↑^a

-0.53

↓^a

PC(20:4/20:4)

0.71

↑^b

-0.71

↓^a

PC(O-16:0/16:0)

0.54

↑^b

-0.54

↓^b

PC(14:0/22:5)

1.06

↑^c

-1.10

↓^b

PI(16:0/20:4)

0.55

↑^b

-0.55

↓^b

TG(18:1/22:6/22:6)

-0.78

↓^c

PC(P-18:1/20:5)

0.57

↑^b

-0.57

↓^b

TG(18:1/18:2/20:0)

-0.78

↓^a

PC(P-18:0/20:4)

0.58

↑^a

-0.58

↓^a

PC(18:0/22:4)

0.83

↑^b

-0.85

↓^b

PC(P-18:1/18:0)

0.59

↑^a

-0.59

↓^a

TG(15:0/18:1/20:3)

-0.87

↓^a

0.83

↑^a

PC(O-14:0/16:0)

0.63

↑^b

-0.63

↓^b

TG(15:0/16:0/20:4)

-0.90

↓^a

0.91

↑^a

PE(P-18:0/18:2)

0.64

↑^a

-0.64

↓^a

CE(22:4)

1.67

↑^b

1.07

↑^a

PC(16:0/18:0)

0.68

↑^a

-0.68

↓^a

PC(O-16:0/18:1)

0.73

↑^b

-0.76

↓^b

PC(22:1/20:3)

0.68

↑^b

-0.68

↓^b

TG(18:1/20:0/22:4)

-0.52

↓^a

PE(P-16:0/22:4)

0.68

↑^b

-0.69

↓^b

TG(15:0/18:1/22:5)

-0.78

↓^a

0.81

↑^a

PC(22:1/20:4)

0.69

↑^a

-0.70

↓^a

PC(20:5/22:5)

1.06

↑^a

PC(P-16:0/18:3)

0.83

↑^b

-0.83

↓^b

SM(d18:2/16:0)

0.82

↑^b

-0.79

↓^a

PE(P-16:0/22:6)

0.94

↑^b

-0.94

↓^b

CE(22:5)

1.41

↑^c

-0.77

↓^a

PI(16:0/16:1)

1.06

↑^a

-1.06

↓^a

PC(P-16:0/20:4)

0.64

↑^c

-0.56

↓^b

PC(16:1/14:0)

1.06

↑^a

-1.06

↓^a

PC(14:0/20:4)

1.11

↑^b

-1.16

↓^b

CE(18:3)

1.07

↑^b

-1.07

↓^b

PC(P-20:0/18:3)

0.62

↑^c

LysoPE(22:6/0:0)

1.07

↑^b

-1.07

↓^b

PC(18:0/18:0)

0.76

↑^a

-0.94

↓^a

PE(P-18:0/22:6)

1.08

↑^b

-1.08

↓^b

PC(P-18:0/20:5)

0.68

↑^b

-0.72

↓^b

GalCer(d18:1/22:0)

1.21

↑^b

-1.20

↓^b

TG(18:2/22:6/20:5)

-0.56

↓^b

-0.88

↓^b

GalCer(d18:1/24:1)

1.23

↑^b

-1.23

↓^b

PC(P-18:0/22:6)

0.67

↑^b

-0.72

↓^a

LysoPC(22:5)

1.31

↑^a

-1.31

↓^a

CE(20:5)

1.00

↑^c

0.95

↑^b

GalCer(d18:1/24:0)

1.33

↑^c

-1.33

↓^c

DG(18:2/22:6/0:0)

-0.95

↓^b

1.08

↑^c

GalCer(d18:1/23:0)

1.37

↑^b

-1.37

↓^b

Eicosadienoic acid

-0.72

↓^c

0.55

↑^b

TG(18:0/18:2/20:0)

-0.94

↓^a

Nonadeca-10-enoic acid

-0.58

↓^a

TG(14:0/20:5/22:5)

-0.62

↓^a

DG(18:1/20:5/0:0)

-0.68

↓^a

-0.62

↓^b

CE(20:3)

0.57

↑^b

DG(16:0/20:4/0:0)

-0.78

↓^a

0.78

↑^a

TG(16:1/20:5/22:6)

-0.83

↓^a

DG(18:2/20:5/0:0)

-0.67

↓^a

0.67

↑^a

CE(20:2)

0.73

↑^a

DG(18:2/22:5/0:0)

-0.61

↓^a

0.61

↑^a

α-Linolenic acid

-0.60

↓^a

No.	Lipid	Model vs control		ACT vs model		No.	Lipid	Model vs control		ACT vs model
1	PC(20:4/18:2)	0.69	↑^b		-0.66	↓^a		38	DG(18:1/22:5/0:0)	-0.57	↓^a	0.57	↑^a
2	TG(16:1/18:1/18:2)	-0.56	↓^a	0.60	↑^a	39	TG(16:0/20:0/22:4)	-0.51	↓^a	0.51	↑^a
3	PC(18:0/22:6)	0.64	↑^a	-	-	40	TG(18:0/18:2/20:4)	-0.50	↓^b	0.50	↑^a
4	TG(16:1/18:1/22:6)	-0.52	↓^a	0.63	↑^b	41	PI(16:0/22:4)	0.29	↑^a	-0.29	↓^a
5	TG(16:1/16:0/22:4)	-0.54	↓^a	0.56	↑^a	42	PI(18:0/22:6)	0.47	↑^a	-0.47	↓^a
6	PC(18:0/22:5)	1.61	↑^a	-1.85	↓^a	43	PC(20:0/20:2)	0.52	↑^a	-0.52	↓^a
7	CE(22:6)	1.16	↑^c	0.76	↑^a	44	CE(16:0)	0.52	↑^a	-0.52	↓^a
8	TG(16:1/18:1/22:2)	-0.78	↓^a	0.73	↑^a	45	PC(O-18:0/16:0)	0.53	↑^a	-0.53	↓^a
9	PC(20:4/20:4)	0.71	↑^b	-0.71	↓^a	46	PC(O-16:0/16:0)	0.54	↑^b	-0.54	↓^b
10	PC(14:0/22:5)	1.06	↑^c	-1.10	↓^b	47	PI(16:0/20:4)	0.55	↑^b	-0.55	↓^b
11	TG(18:1/22:6/22:6)	-0.78	↓^c	-	-	48	PC(P-18:1/20:5)	0.57	↑^b	-0.57	↓^b
12	TG(18:1/18:2/20:0)	-0.78	↓^a	-	-	49	PC(P-18:0/20:4)	0.58	↑^a	-0.58	↓^a
13	PC(18:0/22:4)	0.83	↑^b	-0.85	↓^b	50	PC(P-18:1/18:0)	0.59	↑^a	-0.59	↓^a
14	TG(15:0/18:1/20:3)	-0.87	↓^a	0.83	↑^a	51	PC(O-14:0/16:0)	0.63	↑^b	-0.63	↓^b
15	TG(15:0/16:0/20:4)	-0.90	↓^a	0.91	↑^a	52	PE(P-18:0/18:2)	0.64	↑^a	-0.64	↓^a
16	CE(22:4)	1.67	↑^b	1.07	↑^a	53	PC(16:0/18:0)	0.68	↑^a	-0.68	↓^a
17	PC(O-16:0/18:1)	0.73	↑^b	-0.76	↓^b	54	PC(22:1/20:3)	0.68	↑^b	-0.68	↓^b
18	TG(18:1/20:0/22:4)	-0.52	↓^a	-	-	55	PE(P-16:0/22:4)	0.68	↑^b	-0.69	↓^b
19	TG(15:0/18:1/22:5)	-0.78	↓^a	0.81	↑^a	56	PC(22:1/20:4)	0.69	↑^a	-0.70	↓^a
20	PC(20:5/22:5)	1.06	↑^a	-	-	57	PC(P-16:0/18:3)	0.83	↑^b	-0.83	↓^b
21	SM(d18:2/16:0)	0.82	↑^b	-0.79	↓^a	58	PE(P-16:0/22:6)	0.94	↑^b	-0.94	↓^b
22	CE(22:5)	1.41	↑^c	-0.77	↓^a	59	PI(16:0/16:1)	1.06	↑^a	-1.06	↓^a
23	PC(P-16:0/20:4)	0.64	↑^c	-0.56	↓^b	60	PC(16:1/14:0)	1.06	↑^a	-1.06	↓^a
24	PC(14:0/20:4)	1.11	↑^b	-1.16	↓^b	61	CE(18:3)	1.07	↑^b	-1.07	↓^b
25	PC(P-20:0/18:3)	0.62	↑^c	-	-	62	LysoPE(22:6/0:0)	1.07	↑^b	-1.07	↓^b
26	PC(18:0/18:0)	0.76	↑^a	-0.94	↓^a	63	PE(P-18:0/22:6)	1.08	↑^b	-1.08	↓^b
27	PC(P-18:0/20:5)	0.68	↑^b	-0.72	↓^b	64	GalCer(d18:1/22:0)	1.21	↑^b	-1.20	↓^b
28	TG(18:2/22:6/20:5)	-0.56	↓^b	-0.88	↓^b	65	GalCer(d18:1/24:1)	1.23	↑^b	-1.23	↓^b
29	PC(P-18:0/22:6)	0.67	↑^b	-0.72	↓^a	66	LysoPC(22:5)	1.31	↑^a	-1.31	↓^a
30	CE(20:5)	1.00	↑^c	0.95	↑^b	67	GalCer(d18:1/24:0)	1.33	↑^c	-1.33	↓^c
31	DG(18:2/22:6/0:0)	-0.95	↓^b	1.08	↑^c	68	GalCer(d18:1/23:0)	1.37	↑^b	-1.37	↓^b
32	Eicosadienoic acid	-0.72	↓^c	0.55	↑^b	69	TG(18:0/18:2/20:0)	-	-	-0.94	↓^a
33	Nonadeca-10-enoic acid	-0.58	↓^a	-	-	70	TG(14:0/20:5/22:5)	-	-	-0.62	↓^a
34	DG(18:1/20:5/0:0)	-0.68	↓^a	-0.62	↓^b	71	CE(20:3)	-	-	0.57	↑^b
35	DG(16:0/20:4/0:0)	-0.78	↓^a	0.78	↑^a	72	TG(16:1/20:5/22:6)	-	-	-0.83	↓^a
36	DG(18:2/20:5/0:0)	-0.67	↓^a	0.67	↑^a	73	CE(20:2)	-	-	0.73	↑^a
37	DG(18:2/22:5/0:0)	-0.61	↓^a	0.61	↑^a	74	α-Linolenic acid	-	-	-0.60	↓^a

No.

Lipid

Model vs control

ACT vs model

No.

Lipid

Model vs control

ACT vs model

Log₂FC

Change trend

Log₂FC

Change trend

Log₂FC

Change trend

Log₂FC

Change trend

PC(20:4/18:2)

0.69

↑^b

-0.66

↓^a

DG(18:1/22:5/0:0)

-0.57

↓^a

0.57

↑^a

TG(16:1/18:1/18:2)

-0.56

↓^a

0.60

↑^a

TG(16:0/20:0/22:4)

-0.51

↓^a

0.51

↑^a

PC(18:0/22:6)

0.64

↑^a

TG(18:0/18:2/20:4)

-0.50

↓^b

0.50

↑^a

TG(16:1/18:1/22:6)

-0.52

↓^a

0.63

↑^b

PI(16:0/22:4)

0.29

↑^a

-0.29

↓^a

TG(16:1/16:0/22:4)

-0.54

↓^a

0.56

↑^a

PI(18:0/22:6)

0.47

↑^a

-0.47

↓^a

PC(18:0/22:5)

1.61

↑^a

-1.85

↓^a

PC(20:0/20:2)

0.52

↑^a

-0.52

↓^a

CE(22:6)

1.16

↑^c

0.76

↑^a

CE(16:0)

0.52

↑^a

-0.52

↓^a

TG(16:1/18:1/22:2)

-0.78

↓^a

0.73

↑^a

PC(O-18:0/16:0)

0.53

↑^a

-0.53

↓^a

PC(20:4/20:4)

0.71

↑^b

-0.71

↓^a

PC(O-16:0/16:0)

0.54

↑^b

-0.54

↓^b

PC(14:0/22:5)

1.06

↑^c

-1.10

↓^b

PI(16:0/20:4)

0.55

↑^b

-0.55

↓^b

TG(18:1/22:6/22:6)

-0.78

↓^c

PC(P-18:1/20:5)

0.57

↑^b

-0.57

↓^b

TG(18:1/18:2/20:0)

-0.78

↓^a

PC(P-18:0/20:4)

0.58

↑^a

-0.58

↓^a

PC(18:0/22:4)

0.83

↑^b

-0.85

↓^b

PC(P-18:1/18:0)

0.59

↑^a

-0.59

↓^a

TG(15:0/18:1/20:3)

-0.87

↓^a

0.83

↑^a

PC(O-14:0/16:0)

0.63

↑^b

-0.63

↓^b

TG(15:0/16:0/20:4)

-0.90

↓^a

0.91

↑^a

PE(P-18:0/18:2)

0.64

↑^a

-0.64

↓^a

CE(22:4)

1.67

↑^b

1.07

↑^a

PC(16:0/18:0)

0.68

↑^a

-0.68

↓^a

PC(O-16:0/18:1)

0.73

↑^b

-0.76

↓^b

PC(22:1/20:3)

0.68

↑^b

-0.68

↓^b

TG(18:1/20:0/22:4)

-0.52

↓^a

PE(P-16:0/22:4)

0.68

↑^b

-0.69

↓^b

TG(15:0/18:1/22:5)

-0.78

↓^a

0.81

↑^a

PC(22:1/20:4)

0.69

↑^a

-0.70

↓^a

PC(20:5/22:5)

1.06

↑^a

PC(P-16:0/18:3)

0.83

↑^b

-0.83

↓^b

SM(d18:2/16:0)

0.82

↑^b

-0.79

↓^a

PE(P-16:0/22:6)

0.94

↑^b

-0.94

↓^b

CE(22:5)

1.41

↑^c

-0.77

↓^a

PI(16:0/16:1)

1.06

↑^a

-1.06

↓^a

PC(P-16:0/20:4)

0.64

↑^c

-0.56

↓^b

PC(16:1/14:0)

1.06

↑^a

-1.06

↓^a

PC(14:0/20:4)

1.11

↑^b

-1.16

↓^b

CE(18:3)

1.07

↑^b

-1.07

↓^b

PC(P-20:0/18:3)

0.62

↑^c

LysoPE(22:6/0:0)

1.07

↑^b

-1.07

↓^b

PC(18:0/18:0)

0.76

↑^a

-0.94

↓^a

PE(P-18:0/22:6)

1.08

↑^b

-1.08

↓^b

PC(P-18:0/20:5)

0.68

↑^b

-0.72

↓^b

GalCer(d18:1/22:0)

1.21

↑^b

-1.20

↓^b

TG(18:2/22:6/20:5)

-0.56

↓^b

-0.88

↓^b

GalCer(d18:1/24:1)

1.23

↑^b

-1.23

↓^b

PC(P-18:0/22:6)

0.67

↑^b

-0.72

↓^a

LysoPC(22:5)

1.31

↑^a

-1.31

↓^a

CE(20:5)

1.00

↑^c

0.95

↑^b

GalCer(d18:1/24:0)

1.33

↑^c

-1.33

↓^c

DG(18:2/22:6/0:0)

-0.95

↓^b

1.08

↑^c

GalCer(d18:1/23:0)

1.37

↑^b

-1.37

↓^b

Eicosadienoic acid

-0.72

↓^c

0.55

↑^b

TG(18:0/18:2/20:0)

-0.94

↓^a

Nonadeca-10-enoic acid

-0.58

↓^a

TG(14:0/20:5/22:5)

-0.62

↓^a

DG(18:1/20:5/0:0)

-0.68

↓^a

-0.62

↓^b

CE(20:3)

0.57

↑^b

DG(16:0/20:4/0:0)

-0.78

↓^a

0.78

↑^a

TG(16:1/20:5/22:6)

-0.83

↓^a

DG(18:2/20:5/0:0)

-0.67

↓^a

0.67

↑^a

CE(20:2)

0.73

↑^a

DG(18:2/22:5/0:0)

-0.61

↓^a

0.61

↑^a

α-Linolenic acid

-0.60

↓^a

基于非靶向代谢组学和脂质组学技术的毛蕊花糖苷治疗小儿慢性肾小球肾炎机制研究

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王梦晓 , 罗珂珂 , 田孟尧 , 边宝林 , 杨健 , 杨立新 , 王宏洁 ^* , 周严严 ^*

药学学报 | 研究论文 2025,60(6): 1873-1885

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药学学报 |研究论文 2025 , 60 (6) : 1873 -1885

基于非靶向代谢组学和脂质组学技术的毛蕊花糖苷治疗小儿慢性肾小球肾炎机制研究

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王梦晓, 罗珂珂, 田孟尧, 边宝林, 杨健, 杨立新, 王宏洁^*, 周严严^*

作者信息

中国中医科学院中药研究所, 北京 100700

通讯作者:

王宏洁, Tel: 86-10-64087424, E-mail: hjwang@icmm.ac.cn

周严严, E-mail: yyzhou@icmm.ac.cn

作者简介:

作者贡献:

王梦晓完成实验数据、论文写作与修改; 罗珂珂、田孟尧协助完成实验; 边宝林、杨健、杨立新提供了方法理论支持和建议; 王宏洁、周严严负责实验设计、论文修改。

Study on the mechanism of acteoside in the treatment of pediatric chronic glomerulonephritis based on non-targeted metabolomics and lipidomics techniques

Meng-xiao WANG, Ke-ke LUO, Meng-yao TIAN, Bao-lin BIAN, Jian YANG, Li-xin YANG, Hong-jie WANG^*, Yan-yan ZHOU^*

Affiliations

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China

出版时间: 2025-06-12 doi: 10.16438/j.0513-4870.2025-0090

文章导航

摘要

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基于非靶向代谢组学和脂质组学技术考察毛蕊花糖苷(acteoside, ACT) 对嘌呤霉素氨基核苷(purinomycin aminonucleoside, PAN) 诱导的幼龄大鼠慢性肾小球肾炎(chronic glomerulonephritis, CGN) 血清代谢物的影响, 初步探讨其潜在的作用机制。本实验获得中国中医科学院中药研究所动物福利伦理委员会批准(批准号: 2022B152)。首先采用ELISA试剂盒检测各组大鼠血清细胞因子, 包括IP-10、IL-6、IL-1β、TNF-α, 以评价ACT治疗CGN幼龄大鼠的药效; 整合非靶向代谢组学和脂质组学技术初步揭示其作用机制。结果显示, 与模型组相比, 给药组血清中IP-10、IL-6、IL-1β、TNF-α的水平均显著降低, 说明ACT药效显著。非靶向代谢组学结果显示, 正常组与模型组相比, 共鉴定出23种差异代谢物, 所涉及的通路包括不饱和脂肪酸的生物合成、缬氨酸、亮氨酸和异亮氨酸的生物合成与降解和亚油酸代谢等; 给药组与模型组相比, 共鉴定出25个差异代谢物, 所涉及的通路包括不饱和脂肪酸的生物合成、三羧酸循环、亚油酸代谢等。脂质组学结果显示, 在正常组和模型组中, 共鉴定了68种差异显著的脂质, 所涉及的通路包括omega-3/omega-6脂肪酸合成、T细胞受体和共刺激信号、G蛋白偶联受体激活PKC等通路。经过ACT治疗后, 共有67种差异脂质水平发生显著变化, 上述通路均有显著回调, 还调控了PPARα对脂质代谢的调节和α-亚麻酸和亚油酸代谢等相关通路。差异代谢物和差异脂质相关性分析表明, 代谢物高香草酸、棕榈酸、硫酸吲哚酚以及甘油三酯、磷脂酰胆碱类脂质较为关键。非靶向代谢组学和脂质组学共同调节的通路为不饱和脂肪酸的生物合成和亚油酸代谢。综上所述, ACT主要通过调节甘油三酯和部分磷脂酰胆碱等差异脂质和高香草酸、棕榈酸、硫酸吲哚酚差异代谢物来调控不饱和脂肪酸的生物合成和亚油酸代谢通路以治疗CGN幼龄大鼠。本实验从血清代谢的角度初步阐明了ACT治疗儿童慢性肾小球肾炎的干预机制, 为ACT在CGN患儿中的合理临床应用奠定了坚实的基础。

关键词

非靶向代谢组学 / 脂质组学 / 毛蕊花糖苷 / 小儿慢性肾小球肾炎

Abstract

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This study investigated the effects of acteoside (ACT) on serum metabolites in purinomycin aminonucleoside (PAN)-induced chronic glomerulonephritis (CGN) in young rats using non-targeted metabolomics and lipidomics, and initially explored its potential mechanism of efficacy. The experiment was approved by the Animal Welfare Ethics Committee of Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences (No. 2022B152). Firstly, ELISA kits were used to detect serum cytokines including IP-10, IL-6, IL-1β, and TNF-α in rats of each group to evaluate the efficacy of ACT. Non-targeted metabolomics and lipidomics techniques were used to determine metabolites and lipids in serum, and integrated analysis was conducted to reveal the mechanism. The results showed that compared with the model group, the levels of IP-10, IL-6, IL-1β, and TNF-α in the serum of the ACT groups were significantly reduced, indicating a significant pharmacological effect of ACT. Non-targeted metabolomics results revealed that 23 different metabolites were identified between the control and model groups, involving pathways such as biosynthesis of unsaturated fatty acids, biosynthesis and degradation of valine, leucine, and isoleucine, and linoleic acid metabolism. Between the ACT and model groups, 25 different metabolites were identified, involving pathways such as biosynthesis of unsaturated fatty acids, the TCA cycle, and linoleic acid metabolism. Lipidomics results showed that 68 significantly different lipids were identified between the control and model groups, involving pathways such as omega-3/omega-6 fatty acid synthesis, T-cell receptor and costimulatory signaling, and G-protein-coupled receptor activation of PKC. After ACT treatment, significant changes were observed in 67 differential lipids, with notable reversal in the aforementioned pathways. It also regulated PPARα modulation of lipid metabolism and related pathways such as α-linolenic acid and linoleic acid metabolism. Correlation analysis of differential metabolites and lipids indicated that metabolites such as homovanillic acid, palmitic acid, indoxyl sulfate, as well as triglycerides and phosphatidylcholines were critical. The commonly regulated pathways by non-targeted metabolomics and lipidomics were biosynthesis of unsaturated fatty acids and linoleic acid metabolism. In conclusion, ACT primarily treats CGN in young rats by regulating the biosynthesis of unsaturated fatty acids and linoleic acid metabolism pathways through differential lipids such as triglycerides and some phosphatidylcholines, and differential metabolites such as homovanillic acid, palmitic acid, and indoxyl sulfate. This study initially elucidated the intervention mechanism of ACT in the treatment of pediatric chronic glomerulonephritis from the perspective of serum metabolism, laying a solid foundation for the rational clinical application of ACT in children with CGN.

Key words

non-targeted metabonomics / lipidomics / acteoside / pediatric chronic glomerulonephritis

引用本文

王梦晓, 罗珂珂, 田孟尧, 边宝林, 杨健, 杨立新, 王宏洁, 周严严. 基于非靶向代谢组学和脂质组学技术的毛蕊花糖苷治疗小儿慢性肾小球肾炎机制研究. 药学学报, 2025 , 60 (6) : 1873 -1885 . DOI: 10.16438/j.0513-4870.2025-0090

Meng-xiao WANG, Ke-ke LUO, Meng-yao TIAN, Bao-lin BIAN, Jian YANG, Li-xin YANG, Hong-jie WANG, Yan-yan ZHOU. Study on the mechanism of acteoside in the treatment of pediatric chronic glomerulonephritis based on non-targeted metabolomics and lipidomics techniques[J]. Acta Pharmaceutica Sinica, 2025 , 60 (6) : 1873 -1885 . DOI: 10.16438/j.0513-4870.2025-0090

正文

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慢性肾脏疾病(chronic kidney disease, CKD) 是一种不可逆的肾脏损伤疾病, 可发展为终末期肾病(end stage renal disease, ESRD)。CKD是世界范围内的重大公共卫生问题^[1-4]。近期临床研究显示, 除了先天性和遗传因素导致CKD外, 慢性肾小球肾炎(chronic glomerulonephritis, CGN) 是CKD是首要因素^[5]。目前, 儿童CGN的患病率主要集中在2~12岁, 在过去几十年中发病率逐年上升, 分析其原因可能与环境污染、生活习惯、遗传因素以及感染等相关。小儿CGN对患儿的生活质量和长期预后产生严重影响, 该病主要表现为肾小球的持续性炎症反应, 导致肾小球滤过功能受损。由此可见, 儿童CGN的诊断和治疗仍面临着独特的挑战^[6]。目前治疗药物通常使用激素和免疫抑制剂。然而, 使用西药具有多种不良反应, 患者依从性差, 且容易产生耐药性^[7]。因此, 在中医药理论指导下, 探寻临床疗效确切、不良反应少的中药及有效成分, 对于儿童CGN预防和治疗具有极为关键的现实价值。

毛蕊花糖苷(acteoside, ACT) 是一种水溶性的苯乙醇苷类化合物, 由3, 4-二羟基苯乙醇和咖啡酸两种苷元、葡萄糖和鼠李糖两个糖基构成。ACT是边宝林研究员课题组研发的国家二类新药地黄叶总苷胶囊(国药证字Z20070013) 中的主要活性成分, 占35%~45%, 其具有广泛的生物活性, 包括抗炎^[8-10]、神经保护^[8]、抗癌^[11-13]、促进成骨细胞的增殖和分化^{[14, 15]}等, 且安全、无致畸等不良反应^[16]。近年来, ACT在肾病治疗方面的活性逐渐被发现和认可^{[17, 18]}。本课题组前期完成了ACT提取纯化、代谢规律和治疗肾炎的初步作用机制^[19]。四川美大康药业股份有限公司开展了ACT治疗儿童CGN的临床研究, 初步发现其临床效果显著。然而, 对于ACT治疗儿童CGN的作用机制仍未阐明。因此, 本文使用ELISA检测了ACT干预前后相关细胞因子的变化, 包括IP-10、IL-6、IL-1β、TNF-α。此外, 基于整合非靶向代谢组学和脂质组学技术研究ACT治疗CGN幼龄大鼠潜在的生物标志物, 初步探讨其作用机制。此研究将为ACT在儿童慢性肾小球肾炎的临床应用奠定科学依据, 同时为ACT的新药开发提供前期支撑。

材料与方法

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仪器 Ultimate 3000超高效液相色谱仪(含自动进样器、柱温箱、在线真空脱气机、低压四元梯度泵、PDA检测器)、LTQ Orbitrap Velos Pro质谱仪含高分辨静电场轨道阱质谱、电子喷雾离子源(electronspray ionization, ESI)、Thermo Scientific Heraeus Multifuge X1R高速离心机(美国Thermo Fisher公司); KQ-250B型超声波清洗器(昆山市超声仪器有限公司); XA105-梅特勒-托利多1/10万级电子天平、JA503-1/10千级电子天平(上海舜宇恒平仪器有限公司); IKA MS3 digital涡旋仪(德国IKA公司)。

试剂毛蕊花糖苷为本课题组前期从地黄叶中分离所得(纯度 > 98%)^[20]。嘌呤霉素氨基核苷(purinomycin aminonucleoside, PAN) 购自上海毕得医药科技有限公司(批号BD149557, 250 mg)。大鼠IP-10 (批号JLC5001-202401)、IL-6 (JLC1721-202401)、IL-1β (JLC1704-202401)、TNF-α (JLC2062-202401) ELISA试剂盒购自上海晶抗生物工程有限公司。纯净水购自杭州娃哈哈集团有限公司; 甲醇(色谱级)、乙腈(色谱级)、甲酸(色谱级, 批号212271) 购自美国Thermo Fisher公司。

实验动物 本实验获得中国中医科学院中药研究所动物福利伦理委员会批准(批准号: 2022B152)。3周龄SPF级雄性Sprague-Dawley大鼠, 由北京维通利华实验动物技术有限公司提供, 动物使用许可证号: SCXK (京) 2021-0011。饲养于中国中医科学院中药研究所动物实验中心, 动物房温度: 20 ± 2 ℃, 相对湿度: 60% ± 5%, 12 h光照和黑暗循环。大鼠的饲养和使用均符合中国《实验动物管理条例》。

动物分组及造模 70只SD雄性3周龄大鼠适应性喂养5天, 24 h尿蛋白定量确定无蛋白尿后, 随机分为7组: 正常组、模型组、ACT 5 mg·kg^-1组、ACT 10 mg·kg^-1组、ACT 20 mg·kg^-1组、ACT 40 mg·kg^-1组、阳性药(他克莫司, tacrolimus, FK506) 组, 每组各10只。其造模与治疗方案如图1A所示。实验期间, 观察动物精神情况、行为和毛色有无异常; 每周记录大鼠体重。给药4周后, 20%乌拉坦腹腔注射麻醉大鼠, 剂量为1.0 g·kg^-1, 收集血清, 室温静置2 h后, 4 ℃、3 000 r·min^-1离心10 min, 并储存在-80 ℃超低温冰箱。

血清相关细胞因子测定 按照试剂盒说明书采用ELISA方法测定血清中相关细胞因子的变化, 包括IP-10、IL-6、IL-1β、TNF-α。

基于UHPLC-LTQ-Orbitrap-MS的非靶向代谢组学分析 取血清50 μL, 加入乙腈200 μL, 涡旋混匀3 min, 4 ℃下12 000 r·min^-1离心15 min。每个样品各取10 μL混合制备质控(quality control, QC) 样本, 在检测过程中, 每检测6个样品运行1次QC样本, 用以保证仪器在分析过程中的稳定性。使用ACQUITY UHPLC HSS T3 (2.1 mm × 100 mm, 1.8 μm) 色谱柱; 柱温为35 ℃; 流动相为A (乙腈) 和B (0.1%甲酸-水); 梯度洗脱: 0~2 min, 5%~55% A; 2~10 min, 55%~95% A; 10~15 min, 95% A; 15~15.5 min, 95%~5% A; 15.5~20 min, 5% A; 流速0.3 mL·min^-1; 进样体积: 1 μL。ESI源参数设定如下, 分别使用正离子和负离子扫描模式采集数据, 正离子模式下毛细管温度350 ℃, 毛细管电压35 V, 喷雾电压3.5 kV, 鞘气(N₂) 流速4.55 L·min^-1, 辅助气(N₂) 流速3 L·min^-1; 负离子模式下毛细管电压-35 V, 喷雾电压-3.5 kV, 鞘气(N₂) 流速4.55 L·min^-1, 辅助气(N₂) 流速3 L·min^-1。样品一级质谱在FT模式下进行全扫描(分辨率为30 000, 扫描范围m/z 50~2 000), 二级及三级质谱采用数据依赖性扫描(data dependent scan)。数据采集和分析采用Xcalibur, Metworks和Mass Frontier 7.0软件。

基于UHPLC-Q-Exactive-MS的脂质组学分析 取血清40 μL, 加入甲醇300 μL, 涡旋混匀1 min。加入甲基叔丁基醚1 000 μL, 振摇1 h。加入超纯水250 μL, 涡旋混匀1 min。4 ℃下12 000 r·min^-1离心10 min。取上清液400 μL, 低温真空挥干。加入异丙醇-乙腈(1∶1) 溶液90 μL、25 μg·mL^-1十九烷酸溶液5 μL和15.16 μmol·L^-1 PC 12∶0/13∶0溶液5 μL, 振摇复溶, 待测。QC样本由等体积的各样本均匀混合后得到, 且QC样本的数据采集方法与其他样本完全一致。在检测过程中, 每检测6个样品运行1次QC样品, 用以保证仪器在分析过程中的稳定性。使用ACQUITY UPLC BEH C18 (2.1 mm × 100 mm, 1.7 μm) 色谱柱; 柱温为55 ℃; 正离子模式流动相为A (乙腈-水6∶4, 0.1%甲酸, 5 mmol·L^-1甲酸铵) 和B (乙腈-异丙醇1∶9, 0.1%甲酸, 5 mmol·L^-1甲酸铵); 梯度洗脱: 0~2 min, 100%~70% A; 2~9 min, 70%~30% A; 9~11 min, 30%~5% A; 11~12 min, 5%~0% A; 12~14 min, 0% A; 14~14.1 min, 0%~100% A; 14.1~16 min, 100% A; 流速0.26 mL·min^-1。负离子模式流动相为A (乙腈-水1∶10, 0.04%乙酸, 1 mmol·L^-1乙酸铵) 和B (乙腈-异丙醇1∶1); 梯度洗脱: 0~3 min, 90%~65% A; 3~6 min, 65%~15% A; 6~8 min, 15%~0% A; 8~11 min, 0% A; 11~11.1 min, 0%~90% A; 11.1~13 min, 90% A; 流速0.3 mL·min^-1, 进样体积: 4 μL。ESI源参数设定如下, 分别使用正离子和负离子扫描模式采集数据, 正、负离子的离子源电压分别为3.7和3.5 kV; 毛细管加热温度为320 ℃; 鞘气压力为30 psi, 辅助气压为10 psi; 溶剂加热蒸发温度为300 ℃; 鞘气和辅助气均为N₂; 碰撞气为N₂, 压力为1.5 mTorr。一级全扫描参数为: 分辨率70 000, 自动增益控制目标1×10⁶, 最大隔离时间50 ms, 质荷比扫描范围150~1 500。采用外标法校准质谱质量轴, 质量误差为5 ppm。代谢物鉴定采用dd-MS²扫描模式(数据依赖扫描模式), 参数如下: 分辨率17 500, 自动增益控制目标1×10⁵, 最大隔离时间50 ms, 最多扫描10个离子的二级碎片(动态排除), 质量分离窗口2, 碰撞能30 V, 强度限定1×10⁵。采用Xcalibur 2.2 SP1.48软件控制液质系统, 并进行数据采集。

数据分析及处理 应用Compound Discoverer软件对采集的LC-MS/MS数据进行色谱峰识别、校正和归一化处理, 将得到的数据导入SIMCA 14.1软件, 进行主成分分析(principal component analysis, PCA)、偏最小二乘法判别分析(partial least squares discrimination analysis, PLS-DA) 和正交偏最小二乘法判别分析(orthogonal partial least squares discrimination analysis, OPLS-DA)。分别挑选出VIP ≥ 1及P < 0.05或最大差异倍数 > 1.5的化合物作为对模型有贡献度的标志物。通过MetaboAnalyst 5.0平台和京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG) 等数据库进行注释, 寻找各生物标志物所在的相关代谢通路, 进行通路的富集分析。

多组学联合分析 采用生信分析平台欧易云平台(https://cloud.oebiotech.cn/task/) 将本实验中的差异代谢物和差异脂质进行共表达相关性分析, 根据样本一一对应关系对, 计算两个组学特征之间的相关性, 并将相关性排名前20的代谢产物和脂质绘制矩阵图进行可视化分析。采用生信分析平台基迪奥生物信息云平台(https://www.omicshare.com/) 计算本实验所筛选的差异代谢物与差异脂质之间的相关系数及P值, 将数据导入ChiPlot分析平台(https://www.chiplot.online/), 将相关代谢物和脂质进行网络关联。

统计学分析 采用SPSS软件进行统计分析, 计数资料以

$ \overline{x} $

± s表示, 多组间比较采用单因素方差分析, P < 0.05为差异具有统计学意义。

结果

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1　大鼠血清相关细胞因子的变化

为探讨ACT对CGN幼龄大鼠炎症反应的药效作用, 通过ELISA试剂盒, 对大鼠血清的炎症因子和趋化因子(包括IP-10、IL-6、IL-1β、TNF-α) 进行检测。结果如图1B所示。血清细胞因子, 与模型组相比, ACT显著降低了IP-10、IL-6、IL-1β、TNF-α的水平(P < 0.05)。

2　血清非靶向代谢组学分析

2.1　血清液质图谱分析

为了深入探讨ACT治疗CGN幼龄大鼠的作用机制,以ACT 20 mg·kg^-1剂量组为例, 对大鼠血清进行非靶向代谢组学和脂质组学检测, 筛选各组差异代谢物和差异脂质, 对差异代谢物和差异脂质进行KEGG功能富集分析; 挖掘ACT治疗儿童CGN的相关通路, 初步阐明其干预机制。

利用UHPLC-Orbitrap MS技术, 在正、负离子模式下对血清样本进行数据采集。为了确保实验结果的准确性, 使用QC样品来评价样品采集过程中系统的稳定性和重复性。对比分析发现三组基峰色谱图在峰形上无明显差异, 正常组和模型组以及模型组和给药组的基峰色谱图在峰强度和相对丰度上有明显差异, 如图2所示。推断大鼠血清内源性代谢物在造模后发生紊乱, 给予ACT后有明显回调趋势。

2.2　代谢图谱分析

采用PCA、PLS-DA和OPLS-DA进行分析结果可视化。PCA分析,见图3A、B, 发现三组明显区分, 血清代谢轮廓呈现明显的组间离散趋势, 表明各组大鼠血清中的代谢物总体分布趋势和组间样本的差异度均出现改变。QC样本聚集良好, 说明系统重复性稳定。

大鼠血清在正、负离子模式下进行PLS-DA, 见图3C、D, 正离子模式下, R²X = 0.359, Q² = 0.294; 负离子模式下, R²X = 0.533, Q² = 0.687。各组之间有明显的区分, 说明各组大鼠的血清内源性代谢物有明显差异, 可以进一步分析差异代谢物。同时进行了模型验证, 显示Q²截距小于0, 未发现过拟合现象, 模型可靠, 见图3E、F。

采用OPLS-DA对正常组和模型组、模型组和给药组进行进一步的系统分析, 见图3G~J。正常组和模型组在正离子模式下, R²X = 0.912, Q² = 0.687; 在负离子模式下, R²X = 0.473, Q² = 0.952。模型组和给药组在正离子模式下, R²X = 0.887, Q² = 0.680; 在负离子模式下, R²X = 0.384, Q² = 0.816。以VIP ≥ 1及P < 0.05或最大差异倍数 > 1.5为标准, 筛选血清中潜在的差异代谢物。

2.3　ACT调节CGN幼龄大鼠的血清代谢紊乱

对正常组和模型组、模型组和ACT组进行差异代谢物分析,见图4A、B。筛选VIP ≥ 1, P < 0.05的代谢物, 基于人类代谢组数据库(human metabolome database, HMDB), 在正常组和模型组中, 共鉴定了23种差异显著的代谢物。经过ACT治疗后, 共有25种差异代谢物水平发生显著变化。具体结果见表1。为了阐明ACT对CGN起作用的代谢通路, 将这些差异代谢物导入代谢分析数据库进行分析。KEGG功能富集分析显示, CGN幼龄大鼠不饱和脂肪酸的生物合成、缬氨酸、亮氨酸和异亮氨酸的生物合成、亚油酸代谢和缬氨酸、亮氨酸和异亮氨酸的降解等代谢通路调控异常。而经ACT干预后不饱和脂肪酸的生物合成代谢通路显著回调。同时, ACT还调控了TCA循环、丙氨酸、天冬氨酸和谷氨酸代谢、亚油酸代谢等代谢通路, 见图4C、D。

3　ACT改善CGN幼龄大鼠引起的血清脂质组学特征

3.1　脂质图谱分析

非靶向脂质组学分析同样对血清样本数据进行PCA、PLS-DA和OPLS-DA可视化分析。PCA分析见图5A、B, 发现三组明显区分, 血清代谢轮廓呈现明显的组间离散趋势, 表明各组大鼠血清中的脂质总体分布趋势和组间样本的差异度均出现改变。

大鼠血清在正、负离子模式下进行PLS-DA, 见图5C、D, 正离子模式下, 正常组、模型组和ACT给药组之间的PLS-DA评分参数分别为R²X = 0.495, Q² = 0.172; 负离子模式下, R²X = 0.728, Q² = 0.561。并进行了模型验证, 显示Q²截距小于0, 未过拟合, 模型可靠, 见图5E、F。

继续使用OPLS-DA对正常组和模型组、模型组和给药组进行进一步系统分析, 见图5G~J。正常组和模型组在正离子模式下, R²X = 0.891, Q² = 0.821; 在负离子模式下, R²X = 0.726, Q² = 0.504。模型组和给药组在正离子模式下, R²X = 0.94, Q² = 0.824; 在负离子模式下, R²X = 0.566, Q² = 0.467。以VIP ≥ 1及P < 0.05或最大差异倍数 > 1.5为标准, 筛选血清中潜在的差异脂质。

3.2　ACT调节CGN幼龄大鼠的血清脂质紊乱

对正常组和模型组、模型组和ACT组进行差异脂质分析,见图6A、B。筛选VIP ≥ 1, P < 0.05的化合物, 基于HMDB数据库, 在正常组和模型组中, 共鉴定了68种差异显著的脂质。经过ACT治疗后, 共有67种差异脂质水平发生显著变化, 见表2。由热图可知, ACT对CGN幼龄大鼠的治疗作用主要与对甘油三酯(triglyceride, TG)、甘油二酯(diglycerol, DG) 和磷脂酰胆碱(phosphatidylcholine, PC) 的调节作用相关。同时, 为了阐明ACT对CGN起作用的相关通路, 将这些差异脂质导入脂质分析数据库进行分析。通路富集分析显示, CGN幼龄大鼠omega-3/omega-6脂肪酸合成、T细胞受体和共刺激信号、G蛋白偶联受体激活PKC、Ⅰ型状肾细胞癌中的MET、胰岛素信号等通路调控异常。而经ACT干预后上述通路均有显著回调。此外, ACT还调控了PPARα对脂质代谢的调节和α-亚麻酸和亚油酸代谢等相关通路, 见图6C、D。

4　ACT调节CGN幼龄大鼠的差异代谢物和差异脂质相关性分析

将本实验中的差异代谢物和差异脂质进行共表达相关性分析, 排名前20的代谢产物和脂质绘制矩阵图, 如图7A所示, 前20所筛选出的脂质基本为TG和PC类, 说明ACT主要调节了CGN幼龄大鼠血清中的TG和PC类脂质, 以改善CGN的症状。同时, 将筛选出差异代谢物和差异脂质相关系数大于0.5或小于-0.5 (P < 0.05) 的代谢物-脂质对, 将其进行网络关联, 如图7B所示。结果表明, 代谢物高香草酸、棕榈酸、硫酸吲哚酚以及TG、PC类脂质较为关键。

讨论

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在儿童期发病的肾小球疾病的诊断和治疗存在着挑战, 目前尚无有效的治疗药物。课题组前期研究发现ACT治疗肾炎疾病疗效显著^[20], 但其作用机制尚未阐明。前期结果显示, ACT可以改善CGN幼龄大鼠的尿蛋白肌酐比值、尿酸等生化指标^[8]。本实验首先采用ELISA试剂盒检测各组大鼠血清细胞因子, 包括IP-10、IL-6、IL-1β、TNF-α, 结果显示, 与模型组相比, ACT显著降低血清中IP-10、IL-6、IL-1β、TNF-α的水平(P < 0.05)。结果说明ACT具有显著抑制炎症反应的药效作用。进一步采用非靶向代谢组学技术和非靶向脂质组学技术对ACT治疗CGN幼龄大鼠的作用机制展开研究。非靶向代谢组学结果显示, 正常组与模型组相比, 共鉴定出23种差异代谢物, 所涉及的通路包括不饱和脂肪酸的生物合成和氨基酸代谢等; 给药组与模型组相比, 共鉴定出25个差异代谢物, 所涉及的通路包括不饱和脂肪酸的生物合成、三羧酸循环、丙氨酸、天冬氨酸和谷氨酸代谢、亚油酸代谢。非靶向代谢组学结果表明, ACT治疗CGN幼龄大鼠与血清中不饱和脂肪酸的生物合成密切相关。进一步对血清脂质代谢进行测定分析。脂质组学结果显示, 在正常组和模型组中, 共鉴定了68种差异显著的脂质, 其中, ACT对CGN幼龄大鼠的治疗作用主要与对TG、DG和PC的调节作用相关。所涉及的通路包括omega-3/omega-6脂肪酸合成、T细胞受体和共刺激信号、G蛋白偶联受体激活PKC、Ⅰ型乳头状肾细胞癌中的MET、胰岛素信号等通路。经过ACT治疗后, 共有67种差异脂质水平发生显著变化, 上述通路均有显著回调, 还调控了PPARα对脂质代谢的调节和α-亚麻酸和亚油酸代谢等相关通路。由此可见, 非靶向代谢组学和脂质组学共同调节的通路为不饱和脂肪酸的生物合成和亚油酸代谢。

流行病学研究表明^[21], 在肾脏疾病状态下, 生物样本中通常缺乏omega-3长链多不饱和脂肪酸, 循环多不饱和脂肪酸有助于保护肾脏功能。有研究表明^[22], omega-3多不饱和脂肪酸对IgA肾病有益, 高饮食摄入omega-3多不饱和脂肪酸可以改善糖尿病肾病。多不饱和脂肪酸, 尤其是亚麻酸和亚油酸的低摄入量与慢性肾脏疾病相关^[23]。在慢性肾小球肾炎发生发展过程中, 亚油酸代谢途径可能发生改变, 其代谢产物如前列腺素、白三烯等炎症介质的生成可能增加。同时其在代谢过程中会产生氧化脂质, 这些炎症介质和氧化脂质会引发肾脏局部的炎症反应, 加剧氧化应激损伤, 导致肾小球损伤、系膜细胞增生、细胞外基质积聚等, 进而加重肾脏病变^[24]。

此外, 差异代谢物和差异脂质的网络关联分析表明, 代谢物高香草酸、棕榈酸、硫酸吲哚酚以及TG、PC类脂质较为关键。高香草酸是由邻苯二酚O-甲基转移酶或单胺氧化酶/醛脱氢酶产生的一种稳定的多巴胺代谢物。研究表明, ESRD患者血浆中的高香草酸水平升高, 而糖尿病肾病患者尿液中的高香草酸水平降低, 说明高香草酸水平与慢性肾小球肾炎肾功能受损密切相关^{[25, 26]}。文献^{[27, 28]}报道, 棕榈酸可诱导人足细胞损伤和肾小管内质网应激等。目前已经明确, 硫酸吲哚酚具有一定的肾脏毒性, 与CKD的加速进展有关。动物实验和体外研究均表明了硫酸吲哚酚与肾纤维化增加和氧化应激存在密切联系。多项研究报道, 硫酸吲哚酚对肾脏近端小管细胞产生细胞毒性; 临床研究表明, 硫酸吲哚酚的积累可能导致肾功能不全和不良心血管事件^[29]。相关性分析发现ACT主要调节了TG和PC类脂质的水平。多项研究表明^[30-32], 甘油三酯葡萄糖指数与CKD风险呈非线性相关, 较高的甘油三酯葡萄糖指数可增加CKD风险。文献^[33]报道, CKD可导致PC代谢紊乱, PC代谢失调与CKD病理有关。

综上所述, 本研究通过整合非靶向代谢组学和脂质组学技术, 初步阐明了ACT治疗小儿慢性肾小球肾炎的干预机制, ACT主要通过调节TG和部分PC等差异脂质和高香草酸、棕榈酸、硫酸吲哚酚差异代谢物来调控不饱和脂肪酸的生物合成和亚油酸代谢通路以治疗CGN幼龄大鼠。此为ACT在CGN患儿中的合理临床应用奠定了坚实的基础。与此同时, ACT调控不饱和脂肪酸的生物合成和亚油酸代谢通路的关键靶点及ACT通过何种程序性细胞死亡过程调控高香草酸、棕榈酸、硫酸吲哚酚等差异代谢物的紊乱尚未明确, 诸如此类科学问题的解决仍需多学科技术手段进一步探讨。

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2025年第60卷第6期

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doi: 10.16438/j.0513-4870.2025-0090

接收时间：2025-01-25
首发时间：2026-09-20
出版时间：2025-06-12

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收稿日期：2025-01-25
修回日期：2025-04-28

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中国中医科学院中药研究所, 北京 100700

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王宏洁, Tel: 86-10-64087424, E-mail: hjwang@icmm.ac.cn

周严严, E-mail: yyzhou@icmm.ac.cn

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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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No.	Metabolite	Model vs control		ACT vs model
1	Docosahexaenoic acid	-0.51	↓^c		1.11	↑^c
2	Osbond acid	0.65	↑^c	-0.086	↓^b
3	Cholesterol sulfate	-0.41	↓^c	0.80	↑^a
4	3-Indoxyl sulphate	0.52	↑^c	-0.009 3	↓^b
5	Deoxycholic acid	-0.75	↓^b	0.66	↑^b
6	L-α-Lysophosphatidylcholine	0.25	↑^c	-	-
7	16-Hydroxyhexadecanoic acid	0.94	↑^b	-	-
8	Linoleic acid	-0.12	↓^b	-0.006 2	↓^a
9	Sulfoglycolithocholic acid	-0.088	↓^b	0.12	↑^c
10	Allantoin	1.12	↑^b	-0.26	↓^a
11	2-Pentadecanone	-0.54	↓^a	-	-
12	Isodesmosine	-1.62	↓^c	0.21	↑^c
13	D-Gluconic acid	0.51	↑^a	-0.021	↓^a
14	5-Methoxyindoleacetic acid	-0.011	↓^c	-	-
15	Palmitic acid	0.64	↑^a	-	-
16	Arachidic acid	0.065	↑^b	-	-
17	Ferulic acid 4-sulfate	-2.50	↓^b	0.25	↑^b
18	D-Tryptophan	2.59	↑^a	0.49	↑^a
19	N-Acetyl-9-O-acetylneuraminic acid	0.91	↑^c	-0.062	↓^c
20	Homovanillic acid	3.41	↑^c	-0.088	↓^c
21	2-Keto-glutaramic acid	-1.27	↓^b	-0.85	↓^b
22	IpA	-1.18	↓^c	-0.42	↓^c
23	N-Arachidonylglycine	-1.00	↓^b	-0.98	↓^b
24	Ethyl eicosapentaenoic acid	-	-	-0.076	↓^b
25	Malic acid	-	-	1.16	↑^a
26	D-(-)-Erythrose	-	-	-0.42	↓^b
27	Citric acid	-	-	0.080	↑^b
28	7-Ketodeoxycholic acid	-	-	-0.34	↓^a
29	N-Undecanoylglycine	-	-	-0.17	↓^a
30	Glycochenodeoxycholic acid	-	-	1.25	↑^b
31	Decylubiquinone	-	-	0.93	↑^c

No.

Metabolite

Model vs control

ACT vs model

Log₂FC

Change trend

Log₂FC

Change trend

Docosahexaenoic acid

-0.51

↓^c

1.11

↑^c

Osbond acid

0.65

↑^c

-0.086

↓^b

Cholesterol sulfate

-0.41

↓^c

0.80

↑^a

3-Indoxyl sulphate

0.52

↑^c

-0.009 3

↓^b

Deoxycholic acid

-0.75

↓^b

0.66

↑^b

L-α-Lysophosphatidylcholine

0.25

↑^c

16-Hydroxyhexadecanoic acid

0.94

↑^b

Linoleic acid

-0.12

↓^b

-0.006 2

↓^a

Sulfoglycolithocholic acid

-0.088

↓^b

0.12

↑^c

Allantoin

1.12

↑^b

-0.26

↓^a

2-Pentadecanone

-0.54

↓^a

Isodesmosine

-1.62

↓^c

0.21

↑^c

D-Gluconic acid

0.51

↑^a

-0.021

↓^a

5-Methoxyindoleacetic acid

-0.011

↓^c

Palmitic acid

0.64

↑^a

Arachidic acid

0.065

↑^b

Ferulic acid 4-sulfate

-2.50

↓^b

0.25

↑^b

D-Tryptophan

2.59

↑^a

0.49

↑^a

N-Acetyl-9-O-acetylneuraminic acid

0.91

↑^c

-0.062

↓^c

Homovanillic acid

3.41

↑^c

-0.088

↓^c

2-Keto-glutaramic acid

-1.27

↓^b

-0.85

↓^b

IpA

-1.18

↓^c

-0.42

↓^c

N-Arachidonylglycine

-1.00

↓^b

-0.98

↓^b

Ethyl eicosapentaenoic acid

-0.076

↓^b

Malic acid

1.16

↑^a

D-(-)-Erythrose

-0.42

↓^b

Citric acid

0.080

↑^b

7-Ketodeoxycholic acid

-0.34

↓^a

N-Undecanoylglycine

-0.17

↓^a

Glycochenodeoxycholic acid

1.25

↑^b

Decylubiquinone

0.93

↑^c

No.	Lipid	Model vs control		ACT vs model		No.	Lipid	Model vs control		ACT vs model
1	PC(20:4/18:2)	0.69	↑^b		-0.66	↓^a		38	DG(18:1/22:5/0:0)	-0.57	↓^a	0.57	↑^a
2	TG(16:1/18:1/18:2)	-0.56	↓^a	0.60	↑^a	39	TG(16:0/20:0/22:4)	-0.51	↓^a	0.51	↑^a
3	PC(18:0/22:6)	0.64	↑^a	-	-	40	TG(18:0/18:2/20:4)	-0.50	↓^b	0.50	↑^a
4	TG(16:1/18:1/22:6)	-0.52	↓^a	0.63	↑^b	41	PI(16:0/22:4)	0.29	↑^a	-0.29	↓^a
5	TG(16:1/16:0/22:4)	-0.54	↓^a	0.56	↑^a	42	PI(18:0/22:6)	0.47	↑^a	-0.47	↓^a
6	PC(18:0/22:5)	1.61	↑^a	-1.85	↓^a	43	PC(20:0/20:2)	0.52	↑^a	-0.52	↓^a
7	CE(22:6)	1.16	↑^c	0.76	↑^a	44	CE(16:0)	0.52	↑^a	-0.52	↓^a
8	TG(16:1/18:1/22:2)	-0.78	↓^a	0.73	↑^a	45	PC(O-18:0/16:0)	0.53	↑^a	-0.53	↓^a
9	PC(20:4/20:4)	0.71	↑^b	-0.71	↓^a	46	PC(O-16:0/16:0)	0.54	↑^b	-0.54	↓^b
10	PC(14:0/22:5)	1.06	↑^c	-1.10	↓^b	47	PI(16:0/20:4)	0.55	↑^b	-0.55	↓^b
11	TG(18:1/22:6/22:6)	-0.78	↓^c	-	-	48	PC(P-18:1/20:5)	0.57	↑^b	-0.57	↓^b
12	TG(18:1/18:2/20:0)	-0.78	↓^a	-	-	49	PC(P-18:0/20:4)	0.58	↑^a	-0.58	↓^a
13	PC(18:0/22:4)	0.83	↑^b	-0.85	↓^b	50	PC(P-18:1/18:0)	0.59	↑^a	-0.59	↓^a
14	TG(15:0/18:1/20:3)	-0.87	↓^a	0.83	↑^a	51	PC(O-14:0/16:0)	0.63	↑^b	-0.63	↓^b
15	TG(15:0/16:0/20:4)	-0.90	↓^a	0.91	↑^a	52	PE(P-18:0/18:2)	0.64	↑^a	-0.64	↓^a
16	CE(22:4)	1.67	↑^b	1.07	↑^a	53	PC(16:0/18:0)	0.68	↑^a	-0.68	↓^a
17	PC(O-16:0/18:1)	0.73	↑^b	-0.76	↓^b	54	PC(22:1/20:3)	0.68	↑^b	-0.68	↓^b
18	TG(18:1/20:0/22:4)	-0.52	↓^a	-	-	55	PE(P-16:0/22:4)	0.68	↑^b	-0.69	↓^b
19	TG(15:0/18:1/22:5)	-0.78	↓^a	0.81	↑^a	56	PC(22:1/20:4)	0.69	↑^a	-0.70	↓^a
20	PC(20:5/22:5)	1.06	↑^a	-	-	57	PC(P-16:0/18:3)	0.83	↑^b	-0.83	↓^b
21	SM(d18:2/16:0)	0.82	↑^b	-0.79	↓^a	58	PE(P-16:0/22:6)	0.94	↑^b	-0.94	↓^b
22	CE(22:5)	1.41	↑^c	-0.77	↓^a	59	PI(16:0/16:1)	1.06	↑^a	-1.06	↓^a
23	PC(P-16:0/20:4)	0.64	↑^c	-0.56	↓^b	60	PC(16:1/14:0)	1.06	↑^a	-1.06	↓^a
24	PC(14:0/20:4)	1.11	↑^b	-1.16	↓^b	61	CE(18:3)	1.07	↑^b	-1.07	↓^b
25	PC(P-20:0/18:3)	0.62	↑^c	-	-	62	LysoPE(22:6/0:0)	1.07	↑^b	-1.07	↓^b
26	PC(18:0/18:0)	0.76	↑^a	-0.94	↓^a	63	PE(P-18:0/22:6)	1.08	↑^b	-1.08	↓^b
27	PC(P-18:0/20:5)	0.68	↑^b	-0.72	↓^b	64	GalCer(d18:1/22:0)	1.21	↑^b	-1.20	↓^b
28	TG(18:2/22:6/20:5)	-0.56	↓^b	-0.88	↓^b	65	GalCer(d18:1/24:1)	1.23	↑^b	-1.23	↓^b
29	PC(P-18:0/22:6)	0.67	↑^b	-0.72	↓^a	66	LysoPC(22:5)	1.31	↑^a	-1.31	↓^a
30	CE(20:5)	1.00	↑^c	0.95	↑^b	67	GalCer(d18:1/24:0)	1.33	↑^c	-1.33	↓^c
31	DG(18:2/22:6/0:0)	-0.95	↓^b	1.08	↑^c	68	GalCer(d18:1/23:0)	1.37	↑^b	-1.37	↓^b
32	Eicosadienoic acid	-0.72	↓^c	0.55	↑^b	69	TG(18:0/18:2/20:0)	-	-	-0.94	↓^a
33	Nonadeca-10-enoic acid	-0.58	↓^a	-	-	70	TG(14:0/20:5/22:5)	-	-	-0.62	↓^a
34	DG(18:1/20:5/0:0)	-0.68	↓^a	-0.62	↓^b	71	CE(20:3)	-	-	0.57	↑^b
35	DG(16:0/20:4/0:0)	-0.78	↓^a	0.78	↑^a	72	TG(16:1/20:5/22:6)	-	-	-0.83	↓^a
36	DG(18:2/20:5/0:0)	-0.67	↓^a	0.67	↑^a	73	CE(20:2)	-	-	0.73	↑^a
37	DG(18:2/22:5/0:0)	-0.61	↓^a	0.61	↑^a	74	α-Linolenic acid	-	-	-0.60	↓^a

No.

Lipid

Model vs control

ACT vs model

No.

Lipid

Model vs control

ACT vs model

Log₂FC

Change trend

Log₂FC

Change trend

Log₂FC

Change trend

Log₂FC

Change trend

PC(20:4/18:2)

0.69

↑^b

-0.66

↓^a

DG(18:1/22:5/0:0)

-0.57

↓^a

0.57

↑^a

TG(16:1/18:1/18:2)

-0.56

↓^a

0.60

↑^a

TG(16:0/20:0/22:4)

-0.51

↓^a

0.51

↑^a

PC(18:0/22:6)

0.64

↑^a

TG(18:0/18:2/20:4)

-0.50

↓^b

0.50

↑^a

TG(16:1/18:1/22:6)

-0.52

↓^a

0.63

↑^b

PI(16:0/22:4)

0.29

↑^a

-0.29

↓^a

TG(16:1/16:0/22:4)

-0.54

↓^a

0.56

↑^a

PI(18:0/22:6)

0.47

↑^a

-0.47

↓^a

PC(18:0/22:5)

1.61

↑^a

-1.85

↓^a

PC(20:0/20:2)

0.52

↑^a

-0.52

↓^a

CE(22:6)

1.16

↑^c

0.76

↑^a

CE(16:0)

0.52

↑^a

-0.52

↓^a

TG(16:1/18:1/22:2)

-0.78

↓^a

0.73

↑^a

PC(O-18:0/16:0)

0.53

↑^a

-0.53

↓^a

PC(20:4/20:4)

0.71

↑^b

-0.71

↓^a

PC(O-16:0/16:0)

0.54

↑^b

-0.54

↓^b

PC(14:0/22:5)

1.06

↑^c

-1.10

↓^b

PI(16:0/20:4)

0.55

↑^b

-0.55

↓^b

TG(18:1/22:6/22:6)

-0.78

↓^c

PC(P-18:1/20:5)

0.57

↑^b

-0.57

↓^b

TG(18:1/18:2/20:0)

-0.78

↓^a

PC(P-18:0/20:4)

0.58

↑^a

-0.58

↓^a

PC(18:0/22:4)

0.83

↑^b

-0.85

↓^b

PC(P-18:1/18:0)

0.59

↑^a

-0.59

↓^a

TG(15:0/18:1/20:3)

-0.87

↓^a

0.83

↑^a

PC(O-14:0/16:0)

0.63

↑^b

-0.63

↓^b

TG(15:0/16:0/20:4)

-0.90

↓^a

0.91

↑^a

PE(P-18:0/18:2)

0.64

↑^a

-0.64

↓^a

CE(22:4)

1.67

↑^b

1.07

↑^a

PC(16:0/18:0)

0.68

↑^a

-0.68

↓^a

PC(O-16:0/18:1)

0.73

↑^b

-0.76

↓^b

PC(22:1/20:3)

0.68

↑^b

-0.68

↓^b

TG(18:1/20:0/22:4)

-0.52

↓^a

PE(P-16:0/22:4)

0.68

↑^b

-0.69

↓^b

TG(15:0/18:1/22:5)

-0.78

↓^a

0.81

↑^a

PC(22:1/20:4)

0.69

↑^a

-0.70

↓^a

PC(20:5/22:5)

1.06

↑^a

PC(P-16:0/18:3)

0.83

↑^b

-0.83

↓^b

SM(d18:2/16:0)

0.82

↑^b

-0.79

↓^a

PE(P-16:0/22:6)

0.94

↑^b

-0.94

↓^b

CE(22:5)

1.41

↑^c

-0.77

↓^a

PI(16:0/16:1)

1.06

↑^a

-1.06

↓^a

PC(P-16:0/20:4)

0.64

↑^c

-0.56

↓^b

PC(16:1/14:0)

1.06

↑^a

-1.06

↓^a

PC(14:0/20:4)

1.11

↑^b

-1.16

↓^b

CE(18:3)

1.07

↑^b

-1.07

↓^b

PC(P-20:0/18:3)

0.62

↑^c

LysoPE(22:6/0:0)

1.07

↑^b

-1.07

↓^b

PC(18:0/18:0)

0.76

↑^a

-0.94

↓^a

PE(P-18:0/22:6)

1.08

↑^b

-1.08

↓^b

PC(P-18:0/20:5)

0.68

↑^b

-0.72

↓^b

GalCer(d18:1/22:0)

1.21

↑^b

-1.20

↓^b

TG(18:2/22:6/20:5)

-0.56

↓^b

-0.88

↓^b

GalCer(d18:1/24:1)

1.23

↑^b

-1.23

↓^b

PC(P-18:0/22:6)

0.67

↑^b

-0.72

↓^a

LysoPC(22:5)

1.31

↑^a

-1.31

↓^a

CE(20:5)

1.00

↑^c

0.95

↑^b

GalCer(d18:1/24:0)

1.33

↑^c

-1.33

↓^c

DG(18:2/22:6/0:0)

-0.95

↓^b

1.08

↑^c

GalCer(d18:1/23:0)

1.37

↑^b

-1.37

↓^b

Eicosadienoic acid

-0.72

↓^c

0.55

↑^b

TG(18:0/18:2/20:0)

-0.94

↓^a

Nonadeca-10-enoic acid

-0.58

↓^a

TG(14:0/20:5/22:5)

-0.62

↓^a

DG(18:1/20:5/0:0)

-0.68

↓^a

-0.62

↓^b

CE(20:3)

0.57

↑^b

DG(16:0/20:4/0:0)

-0.78

↓^a

0.78

↑^a

TG(16:1/20:5/22:6)

-0.83

↓^a

DG(18:2/20:5/0:0)

-0.67

↓^a

0.67

↑^a

CE(20:2)

0.73

↑^a

DG(18:2/22:5/0:0)

-0.61

↓^a

0.61

↑^a

α-Linolenic acid

-0.60

↓^a