Analysis of Mechanism of Yimai Granules in Treatment of Atherosclerosis Based on Bioinformatics

GUAN Le; MIN Dong-yu; WANG Jun-yan; JIU Jun-long; YANG Guan-lin; WANG Qing-feng

doi:10.13422/j.cnki.syfjx.20181402

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Analysis of Mechanism of Yimai Granules in Treatment of Atherosclerosis Based on Bioinformatics

更新时间：2024-01-04

- Analysis of Mechanism of Yimai Granules in Treatment of Atherosclerosis Based on Bioinformatics
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 24, Issue 16, Pages: 82-87(2018)
- 作者机构：
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20181402
  CLC： R285.5
- Published：2018
- 稿件说明：
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GUAN Le, MIN Dong-yu, WANG Jun-yan, et al. Analysis of Mechanism of Yimai Granules in Treatment of Atherosclerosis Based on Bioinformatics[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(16): 82-87.
DOI：

GUAN Le, MIN Dong-yu, WANG Jun-yan, et al. Analysis of Mechanism of Yimai Granules in Treatment of Atherosclerosis Based on Bioinformatics[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(16): 82-87. DOI： 10.13422/j.cnki.syfjx.20181402.

摘要

目的：以生物信息学手段预测临床方剂益脉颗粒的作用靶点，根据靶点基因的调节方式，确定其作用的信号通路，最终确定该方的分子作用机制。方法：采用生物信息学手段对该组方内的全部药物的潜在调控基因进行预测。根据药物的君、臣、佐、使构成，对益脉颗粒内全部作用于动脉粥样硬化（AS）的靶点基因进行韦恩图绘制，将上述重叠的基因定义为靶向基因。考察给药前后AS模型小鼠的血象变化及对应的靶点基因调控方式，以确定该方剂改善AS的机制。实验组共计60只ApoE-/-小鼠，随机分为5组，连续喂养12周；模型组12只，高脂高胆固醇饮食+生理盐水灌胃；益脉颗粒高剂量组12只，高脂高胆固醇饮食+中药高剂量灌胃；益脉颗粒中剂量组12只，高脂高胆固醇饮食+中药中剂量灌胃；益脉颗粒低剂量组12只，高脂高胆固醇饮食+中药低剂量灌胃；阳性组12只，高脂高胆固醇饮食+阿托伐他汀钙片。结果：益脉颗粒可降低小鼠的甘油三酯（TG），总胆固醇（TC），低密度脂蛋白胆固醇（LDL-C）及高密度脂蛋白胆固醇（HDL-C）水平，且与剂量呈正相关；益脉颗粒高剂量组降低TG，TC，LDL-C及HDL-C的水平均弱于阿托伐他汀钙片组。预测发现益脉颗粒的作用靶点包括羧酸酯酶1（CES1），3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR），过氧化物酶体增殖物激活受体（PPAR） D，PPARG，肝X受体α（LXR-α）及三磷酸腺苷结合盒转运体A1（ABCA1）。结论：益脉颗粒可通过对CES1，HMGCR，PPARD，PPARG，LXR-α及ABCA1等靶点基因表达的上调，激活相应的信号通路，从而实现对AS的治疗作用。采用生物信息学手段可推测及验证复方的作用靶点，为解释方剂对疾病治疗的作用机制提供了思路。

Abstract

Objective: To predict the targets of Yimai granules by bioinformatics

according to the adjustment of target genes

to determine its signaling pathways and the molecular mechanism of Yimai granules. Method: Bioinformatics was used to predict the potential regulatory genes of all drugs in Yimai granules.According to the principles of formulating prescription

a Venn diagram was drawn for all target genes of Yimai granules that acted on atherosclerosis(AS)

the overlapping genes were defined as target genes.Before and after administration

the hemogram changes of the AS model mice and the corresponding target gene regulation methods were used to determine the mechanism of Yimai granules to improve AS.The experimental group consisted of 60 ApoE-/- mice

they were randomly divided into 5 groups and fed continuously for 12 weeks.Twelve rats in model group were fed with high fat and high cholesterol diet+normal saline by intragastric administration;twelve rats in the high

medium and low dosage groups of Yimai granules were fed with high fat and cholesterol diet+high

medium and low dose of Yimai granules

respectively;twelve rats in the positive group were fed with high fat and high cholesterol diet+atorvastatin calcium tablets. Result: Yimai granules can reduce levels of triglyceride(TG)

total cholesterol(TC)

low density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) in mice

and the effect was positively correlated with the dose of Yimai granules.The lowering of TG

LDL-C and HDL-C in the high-dose group of Yimai granules was weaker than those in the atorvastatin calcium tablets group.The targets of Yimai granules included carboxylesterase 1(CES1)

3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGCR)

peroxisome proliferator-activated receptor(PPAR)D

PPARG

liver X receptor-α(LXR-α) and adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1). Conclusion: Yimai granules can activate the corresponding signaling pathway by up-regulating the expression of target genes of CES1

HMGCR

PPARD

PPARG

LXR-α and ABCA1

so as to achieve the therapeutic effect on AS.Bioinformatics can be used to predict and verify the action targets of formulas

which can provide a method to explain the mechanism of clinical formulas.

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