麦冬提取物治疗2型糖尿病小鼠的血清代谢组学研究<sup>*</sup>

doi:10.13523/j.cb.2209009

中国生物工程杂志

2022, Vol. 42

Issue (11): 99-108 DOI: 10.13523/j.cb.2209009

生物质资源

麦冬提取物治疗2型糖尿病小鼠的血清代谢组学研究^*

张杰^1,²,林炳锋²,许平翠²,王娜妮²,陈郁^1,^**(

)

1 杭州职业技术学院杭州 310018
2 浙江省中医药研究院杭州 310007

Serum Metabolomics of Ophiopogon japonicus Extract Against Type 2 Diabetes in Mice

ZHANG Jie^1,², LIN Bing-feng², XU Ping-cui², WANG Na-ni², CHEN Yu^1,^**(

)

1 Hangzhou Vocational & Technical College, Hangzhou 310018, China
2 Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, China

全文: PDF(1501 KB) HTML

摘要：

目的:采用代谢组学方法研究麦冬对2型糖尿病(T2DM)小鼠内源性代谢物的影响。方法: 腹腔注射链脲佐菌素建立T2DM小鼠模型。连续4周灌胃给予麦冬水提物后,检测血清中糖尿病相关指标,且以超高效液相色谱-飞行时间质谱联用(UPLC-Q/TOF-MS)技术,研究麦冬对T2DM小鼠血清中代谢物质的影响,分析相关代谢通路。结果: 与正常对照组相比,模型组血清的空腹葡萄糖、总胆固醇、甘油三酯、低密度脂蛋白胆固醇含量显著升高,高密度脂蛋白胆固醇含量显著降低;灌胃给予麦冬水提物后,T2DM小鼠血清中以上指标均明显改善。代谢组学结果显示,正常组与模型组共有43个差异代谢物,富集于18条通路;麦冬提取物明显降低T2DM小鼠的甘油酸、丙二酸半醛和4-羟基苯基丙酮酸含量,差异代谢物富集于泛醌和其他萜类醌生物合成代谢等7条通路。结论: 麦冬水提物具有降低T2DM小鼠血糖和血脂的药效作用,且可能与泛醌和其他萜类醌生物合成等通路有关。

关键词： 代谢组学; 2型糖尿病; 麦冬; 血清; 超高效液相色谱-飞行时间质谱联用技术

Abstract:

Objective: To study the protective mechanism of Ophiopogon japonicus extract on Type 2 diabetes mellitus (T2DM) based on metabolomics. Methods: The T2DM mouse model was established by intraperitoneal injection of streptozotocin. Mice were orally administrated with the aqueous extract of Ophiopogon japonicu for 4 weeks. The diabetic phenotypes in serum were measured. Changes in serum metabolites were determined by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS). Results: Compared with the control group, the fasting glucose, total cholesterol, triglyceride, and low-density lipoprotein cholesterol were increased in the model group, while the high-density lipoprotein cholesterol decreased significantly, and the above indexes were reversed after treatment of Ophiopogon japonicus extract. The metabonomic results showed that 43 differential metabolites were found between the control group and the model group. These metabolites were enriched in 18 pathways. Ophiopogon japonicus extract significantly decreased the content of glyceric acid, malonic semialdehyde, and 4-hydroxyphenylpyruvic acid in T2DM mice. Ophiopogon japonicus extract could regulate 7 pathways, such as ubiquinone and other terpenoid-quinone biosynthesis. Conclusion: The hypoglycemic and lipid-lowering effect of Ophiopogon on T2DM may be related to ubiquinone and other terpenoid-quinone biosynthesis.

Key words: Metabonomics Type 2 diabetes Ophiopogon japonicas Serum UPLC-Q/TOF-MS

收稿日期: 2022-09-03 出版日期: 2022-12-07

ZTFLH:

Q819

基金资助: *国家自然科学基金(81973447);杭州市农业与社会发展科研项目(20201203B130)

通讯作者: **电子信箱:1181411591@qq.com

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引用本文:

张杰, 林炳锋, 许平翠, 王娜妮, 陈郁. 麦冬提取物治疗2型糖尿病小鼠的血清代谢组学研究^*[J]. 中国生物工程杂志, 2022, 42(11): 99-108.

ZHANG Jie, LIN Bing-feng, XU Ping-cui, WANG Na-ni, CHEN Yu. Serum Metabolomics of Ophiopogon japonicus Extract Against Type 2 Diabetes in Mice. China Biotechnology, 2022, 42(11): 99-108.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2209009 或 https://manu60.magtech.com.cn/biotech/CN/Y2022/V42/I11/99

图1 麦冬对T2DM模型小鼠血清中FBG、TC、TG、LDL-C和HDL-C水平的影响

图2 PCA 3D得分图

图3 PLS-DA得分图

图4 OPLS-DA得分图和Permutation验证图

编号	HMDB号	代谢物		质荷比 (m/z)		保留时间 /min		分子式		加合物		正常组 vs.模型组		模型组 vs.麦冬组
1	HMDB0000700	Hydroxypropionic acid		71.013 8		0.06		C₃H₆O₃		M-H₂O-H		↓^**		↓
2	HMDB0011111	Malonic semialdehyde		87.008 7		9.58		C₃H₄O₃		M-H		↓^*		↑^*
3	HMDB0000139	Glyceric acid		87.008 7		8.01		C₃H₆O₄		M-H₂O-H		↓^*		↑^*
4	HMDB0000630	Cytosine		92.025 3		19.84		C₄H₅N₃O		M-H₂O-H		↑^**		↑
5	HMDB0000718	Isovaleric acid		101.060 7		12.14		C₅H₁₀O₂		M-H		↓^**		↑
6	HMDB0000019	Alpha-ketoisovaleric acid		115.040 0		0.06		C₅H₈O₃		M-H		↓^**		↑
7	HMDB0000227	Mevalonic acid		129.055 7		5.34		C₆H₁₂O₄		M-H₂O-H		↑^**		↓
8	HMDB0001644	D-Xylulose		131.034 9		3.09		C₅H₁₀O₅		M-H₂O-H		↓^**		↑
9	HMDB0006483	D-Aspartic acid		132.030 1		0.05		C₄H₇NO₄		M-H		↓^**		↓
10	HMDB0000157	Hypoxanthine		135.031 3		10.56		C₅H₄N₄O		M-H		↓^**		↑
11	HMDB0000635	Succinylacetone		139.040 0		9.60		C₇H₁₀O₄		M-H₂O-H		↓^**		↑
12	HMDB0000819	Normetanephrine		164.071 7		7.63		C₉H₁₃NO₃		M-H₂O-H		↓		↓^*
13	HMDB0014634	Miglitol		188.092 7		1.88		C₈H₁₇NO₅		M-H₂O-H		↓^**		↓
14	HMDB0000291	Vanillylmandelic acid		197.045 4		9.84		C₉H₁₀O₅		M-H		↓^*		↑
15	HMDB0006059	20-Carboxy-leukotriene B4		347.186 1		9.38		C₂₀H₂₈O₅		M-H20-H		↓^*		↓
16	HMDB0012136	1-Amino-propan-2-ol		76.076 3		0.92		C₃H₉NO		M+H		↑^*		↓
17	HMDB0000097	Choline		86.096 9		1.10		C₅H₁₄NO		M+H-H₂O		↓^**		↓
18	HMDB0033827	(2E)-2-Heptenal		95.085 9		0.60		C₇H₁₂O		M+H-H₂O		↑^**		↓
19	HMDB0002362	2,4-Diaminobutyric acid		101.071 2		14.00		C₄H₁₀N₂O₂		M+H-H₂O		↓^*		↑
20	HMDB0000459	3-Methylcrotonylglycine		140.070 4		10.70		C₇H₁₁NO₃		M+H-H₂O		↓^**		↓
21	HMDB0000182	L-Lysine		147.112 6		10.59		C₆H₁₄N₂O₂		M+H		↑^*		↑
22	HMDB0000205	Phenylpyruvic acid		165.054 3		0.11		C₉H₈O₃		M+H		↑^*		↑
23	HMDB0000159	L-Phenylalanine		166.086 1		2.91		C₉H₁₁NO₂		M+H		↓^**		↓
24	HMDB0001431	Pyridoxamine		169.096 9		1.09		C₈H₁₂N₂O₂		M+H		↓^**		↑
25	HMDB0000446	N-alpha-acetyl-L-lysine		171.112 5		1.08		C₈H₁₆N₂O₃		M+H-H₂O		↓^**		↓
26	HMDB0000701	Hexanoylglycine		174.112 3		8.11		C₈H₁₅NO₃		M+H		↓^**		↓
27	HMDB0014018	4-Hydroxypropofol		177.127 1		15.79		C₁₂H₁₈O₂		M+H-H₂O		↑^**		↑^*
28	HMDB0000707	4-Hydroxyphenylpyruvic acid		181.049 2		15.68		C₉H₈O₄		M+H		↓^**		↑^*
29	HMDB0000158	L-Tyrosine		182.080 8		7.09		C₉H₁₁NO₃		M+H		↓^**		↑
30	HMDB0001024	Phosphohydroxypyruvic acid		184.985 1		16.48		C₃H₅O₇P		M+H		↓^**		↑
31	HMDB0002302	Indole-3-propionic acid		190.085 9		9.60		C₁₁H₁₁NO₂		M+H		↑^**		↓
32	HMDB0012948	Formyl-5-hydroxykynurenamine		191.080 9		1.11		C₁₀H₁₂N₂O₃		M+H-H₂O		↓^**		↑
33	HMDB0000350	3-Hydroxysebacic acid		201.111 8		10.70		C₁₀H₁₈O₅		M+H-H₂O		↓^**		↑
34	HMDB0013286	N-Undecanoylglycine		213.982 5		19.80		C₁₃H₂₅NO₃		M+H-H₂O		↑^**		↑^*
35	HMDB0011175	Leucylproline		229.154 1		1.08		C₁₁H₂₀N₂O₃		M+H		↓^**		↓
36	HMDB0011170	Gamma-glutamylisoleucine		261.143 9		6.61		C₁₁H₂₀N₂O₅		M+H		↓^**		↓^*
37	HMDB0013133	Methylmalonylcarnitine		262.127 9		1.06		C₁₁H₁₉NO₆		M+H		↑^*		↓
38	HMDB0004701	9,10-Epoxyoctadecenoic acid	279.230 9		14.57		C₁₈H₃₂O₃		M+H-H₂O		↑^**		↓
39	HMDB0000252	Sphingosine	282.278 5		16.11		C₁₈H₃₇NO₂		M+H-H₂O		↓^*		↓
40	HMDB0001388	Alpha-linolenic acid	301.215 0		13.39		C₁₈H₃₀O₂		M+H		↓^*		↑
41	HMDB0001043	Arachidonic acid	305.246 6		14.28		C₂₀H₃₂O₂		M+H		↓^**		↓^*
42	HMDB0000222	Palmitoylcarnitine	400.341 6		17.35		C₂₃H₄₅NO₄		M+H		↑^**		↑
43	HMDB0011760	Cer(d18:0/16:0)	540.534 1		16.33		C₃₄H₆₉NO₃		M+H		↓^**		↑
44	HMDB0010392	LysoPC[20:2(11Z,14Z)/0:0]	548.369 9		14.45		C₂₈H₅₆NO₇P		M+H		↓^**		↓。*

表1 麦冬治疗T2DM潜在生物标志物

图5 空白组与模型组的差异代谢物通路图(a)和麦冬组与模型组的差异物代谢通路图(b)

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