黄芪散对高脂饮食诱导肥胖大鼠肝脏内质网应激信号通路的影响

李艳; 曹美群; 陶文聪; 李卫民; 罗焕敏; 吴正治

doi:10.13422/j.cnki.syfjx.20191901

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黄芪散对高脂饮食诱导肥胖大鼠肝脏内质网应激信号通路的影响

经典名方 | 更新时间：2021-02-09

- 黄芪散对高脂饮食诱导肥胖大鼠肝脏内质网应激信号通路的影响
- Effect of Huangqisan on Endoplasmic Reticulum Stress Signaling Pathway in Liver Tissues of High-fat Diet-induced Obese Rats
- 中国实验方剂学杂志 2019年25卷第21期页码：6-11
- 作者机构：
  
  1.暨南大学　中西医结合博士后流动站，广州　 510632；
  2.深圳市老年医学研究所，广东　深圳　 518035；
  3.深圳大学　第一附属医院(深圳市第二人民医院)，广东　深圳　 518035；
  4.广州中医药大学　中药学院，广州　 510006
- 作者简介：
  
  李艳，博士，助理研究员，从事中药新药的研究与开发，E-mail：apple2014yan@126.com
  吴正治，博士，教授，从事老年神经系统疾病中西医结合研究，Tel：0755-82530086，E-mail：szwzz001@163.com
- 基金信息：
  
  国家自然科学基金项目(81803867;81574038);广东省科技计划项目(2018A0303130078;2015B020211001);中国博士后科学基金面上项目(2017M622920);深圳市医疗卫生三名工程项目(SZSM201612049);深圳市学科布局项目(JCYJ20180508152437368;JCYJ20170412161254416;JCYJ20170413161352000);国家高技术研究发展技术（863）项目(2014AA020907)
- DOI：10.13422/j.cnki.syfjx.20191901
  中图分类号： R2-0; R22; R285.5; R289
- 收稿日期：2019-03-13，
  
  网络出版日期：2019-06-19，
  
  纸质出版日期：2019-11-05
- 稿件说明：
移动端阅览
李艳, 曹美群, 陶文聪, 等. 黄芪散对高脂饮食诱导肥胖大鼠肝脏内质网应激信号通路的影响[J]. 中国实验方剂学杂志, 2019,25(21):6-11.

Yan LI, Mei-qun CAO, Wen-cong TAO, et al. Effect of Huangqisan on Endoplasmic Reticulum Stress Signaling Pathway in Liver Tissues of High-fat Diet-induced Obese Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(21): 6-11.
李艳, 曹美群, 陶文聪, 等. 黄芪散对高脂饮食诱导肥胖大鼠肝脏内质网应激信号通路的影响[J]. 中国实验方剂学杂志, 2019,25(21):6-11. DOI： 10.13422/j.cnki.syfjx.20191901.

Yan LI, Mei-qun CAO, Wen-cong TAO, et al. Effect of Huangqisan on Endoplasmic Reticulum Stress Signaling Pathway in Liver Tissues of High-fat Diet-induced Obese Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(21): 6-11. DOI： 10.13422/j.cnki.syfjx.20191901.

摘要

目的：

观察黄芪散对高脂饮食诱导的肥胖大鼠肝脏内质网应激信号通路的影响，并探讨其机制。

方法：

选择雄性SD大鼠，通过高脂饲料连续喂养7周建立肥胖大鼠模型后，将其随机分为模型组，黄芪散低、高剂量组(1.2，2.4 g·kg

－1

)，立普妥组(2 mg·kg

－1

)，模型组和正常组给予等量生理盐水，灌胃给药，连续15周。分别测定各组大鼠的体质量、附睾脂肪系数、肝脏系数；采用生化试剂测定血浆空腹血糖(FPG)，总胆固醇(TC)，甘油三酯(TG)，低密度脂蛋白胆固醇(LDL-C)的水平；采用苏木素-伊红(HE)染色法观察各组大鼠附睾脂肪及肝脏病理变化；同时采用蛋白免疫印迹法(Western blot)检测肝组织中固醇调节元件结合蛋白-1c(SREBP-1c)，蛋白激酶R样内质网激酶(PERK)，肌醇依赖酶1

(IRE1

)，磷酸化IRE1

(p-IRE1

)的蛋白表达水平。

结果：

与正常组比较，模型组大鼠的体质量和肝脏系数显著升高(

0.01)；FPG，TC，TG，LDL-C水平均明显升高(

0.05，

0.01)。模型组大鼠的脂肪细胞和肝细胞体积明显增大，细胞中可见大量脂肪小泡。同时肝组织中内质网应激相关因子SREBP-1c，PERK，IRE1

，p-IRE1

的蛋白表达明显升高(

0.05，

0.01)。与模型组比较，黄芪散高、低剂量组均能明显降低肥胖大鼠的体质量、附睾脂肪系数、肝脏系数和糖脂水平(

0.05，

0.01)，且能明显改善附睾脂肪和肝脏的病变程度。黄芪散高、低剂量组及立普妥组大部分可不同程度地降低肝组织中SREBP-1c，PERK，IRE1

/p-IRE1

的蛋白表达水平(

0.05，

0.01)。

结论：

黄芪散具有调节糖脂代谢、保护肝脏和减轻体质量的作用，其机制可能与调控肝脏内质网应激相关因子SREBP-1c，PERK，IRE1

/p-IRE1

的蛋白表达有关。

Abstract

Objective:

To explore the effect of Huangqisan on endoplasmic reticulum stress signaling pathway in liver tissues of high-fat diet-induced obese rats and its mechanisms.

Method:

Male SD rats were selected and fed with high-fat diet for 7 weeks continuously to establish an obese rat model. Then

the rats were randomly divided into model group

low and high-dose Huangqisan group (1.2

2.4 g·kg

-1

)

and Lipitor group (2 mg·kg

-1

)

and orally administered with drugs for 15 consecutive weeks. The control group and the model group were perfused with the same volume of normal saline. The body weight

epididymal fat coefficient and liver coefficient of each group were determined separately. Fasting plasma glucose (FPG)

total cholesterol (TC)

triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) were determined by biochemical reagent method. The epididymal visceral adipose tissue and liver pathological changes were observed by hematoxylin and eosin (HE) staining. And the protein expression levels of sterol regulation element-binding transcription factor 1 (SREBP-1c)

protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)

inositol requiring enzyme 1 (IRE1

)

p-inositol requiring enzyme 1 (p-IRE1

) in liver tissues were detected by Western blot methods.

Result:

Compared with the control group

the body weight

epididymal fat coefficient and liver coefficient of the model group were significantly increased(

0.01)

and the levels of FPG

TG and LDL-C were also higher than those of the control group(

0.05

0.01). The cell volume of epididymal fat and liver in the model group were enlarged

and numerous fat vesicles were observed in the cells. Meanwhile

the protein expression levels of the endoplasmic reticulum stress-related factors SREBP-1c

PERK

IRE1

/p-IRE1

were increased(

0.05

0.01). Compared with the model group

high-dose and low-dose Huangqisan groups could significantly reduce the body weight

epididymal fat coefficient

liver coefficient and levels of glucose and lipid(

0.05

0.01)

and pathological examination showed that the lesion degrees of epididymal fat and liver tissues were alleviated obviously. In addition

Huangqisan could mostly reduce SREBP-1c

PERK

IRE1

/p-IRE1

protein expression levels to different degrees(

0.05

0.01).

Conclusion:

Huangqisan could regulate the glucose and lipid metabolism

alleviate liver pathology and reduce body weight

and its mechanism was probably related to reduction of SREBP-1c

PERK

IRE1

/p-IRE1

proteins expression levels.

关键词

Keywords

references

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