Effect of Huangqisan on Endoplasmic Reticulum Stress Signaling Pathway in Liver Tissues of High-fat Diet-induced Obese Rats

Yan LI; Mei-qun CAO; Wen-cong TAO; Wei-min LI; Huan-min LUO; Zheng-zhi WU

doi:10.13422/j.cnki.syfjx.20191901

您当前的位置：

首页 >

文章列表页 >

Effect of Huangqisan on Endoplasmic Reticulum Stress Signaling Pathway in Liver Tissues of High-fat Diet-induced Obese Rats

Classic Prescriptions | 更新时间：2021-02-09

- Effect of Huangqisan on Endoplasmic Reticulum Stress Signaling Pathway in Liver Tissues of High-fat Diet-induced Obese Rats
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 21, Pages: 6-11(2019)
- 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：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191901
  CLC： R2-0; R22; R285.5; R289
- Published：05 November 2019，
  
  Published Online：19 June 2019，
  
  Received：13 March 2019，
- 稿件说明：
扫描看全文
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 25(21):6-11(2019)
DOI：

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 25(21):6-11(2019) 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

肥胖黄芪散内质网应激信号通路

Keywords

obesityHuangqisanendoplasmic reticulum stresssignaling pathway

references

Mary J W E. Nutrition, the visceral immune system, and the evolutionary origins of pathogenic obesity [J].PNAS, 2019, 116(3): 723-731.

Hepatology T L G. Obesity management: gastroenterologists take centre stage [J].Lancet Gastroenterol Hepatol, 2017, 2(7): 463.

Elizabeth T C, Lining G, Christine L S, et al. Profound perturbation of the metabolome in obesity is associated with health risk [J].Cell Metab, 2019, 29(2): 488-500.

Ayonrinde O T, Oddy W H, Adams L A, et al. Infant nutrition and maternal obesity influence the risk of non-alcoholic fatty liver disease in adolescents [J].J Hepatol, 2017, 67(3): 568-576.

郝梦娇，党院霞，周欣欣，等．黄芪散对高脂血症大鼠AMPK/ACC/CPT1通路的影响[J]．中国中药杂志，2018，43(12)：2586-2592．

李艳，高英，高颖，等．黄芪散及其拆方对T2DM大鼠胰岛素抵抗及肝组织11β-HSD1，PEPCK的影响[J]．中国实验方剂学杂志，2017，23(15)：136-142．

罗娇艳，王芳，张娟，等．黄芪散对糖脂代谢和骨生物力学指标影响的实验研究[J]．广东药学院学报，2015，31(1)：75-79．

Mikolasevic I, Milic S, Racki S, et al. Nonalcoholic fatty liver disease (NAFLD)-a new cardiovascular risk factor in peritoneal dialysis patients [J].Perit Dial Int, 2016, 36(4): 427-432.

Valentini D, Alisi A, di Camillo C, et al. Nonalcoholic fatty liver disease in italian children with down syndrome: prevalence and correlation with obesity-related features [J].J Pediatr, 2017, 189: 92-97.

DONG L, XING L, TI Z, et al. IRE1-RACK1 axis orchestrates ER stress preconditioning-elicited cytoprotection from ischemia/reperfusion injury in liver [J].J Mol Cell Biol, 2016, 8(2): 144-156.

LI H, ZHOU B, LIU J, et al. Administration of progranulin (PGRN) triggers ER stress and impairs insulin sensitivity via PERK-eIF2α-dependent manner [J].Cell Cycle, 2015, 14(12): 1893-1907.

Woo-Gyun C, Jaeseol H, Ji-Hyeon K, et al. eIF2α phosphorylation is required to prevent hepatocyte death and liver fibrosis in mice challenged with a high fructose diet [J].Nutr Metab (Lond), 2017, doi: 10.1186/s12986-017-0202-6http://doi.org/10.1186/s12986-017-0202-6.

ZHAI X, YAN K, FAN J, et al. The β-catenin pathway contributes to the effects of leptin on SREBP-1c expression in rat hepatic stellate cells and liver fibrosis [J].Br J Pharmacol, 2013, 169(1): 197-212.

XU X, Jae-Seon S, Jong-Gil P, et al. Transcriptional control of hepatic lipid metabolism by SREBP and ChREBP [J].Semin Liver Dis, 2013, 33(4): 301-311.

李雨庭，李诗畅，牛雯颖，等．方剂药理研究的方法与思路[J]．中国实验方剂学杂志，2017，23(21)：229-234．

石格，毛志敏，万毅刚，等．糖尿病肾病足细胞损伤的病理机制及中药的干预作用[J]．中国中药杂志，2016，41(13)：2416-2421．

刘倩，范颖，李新，等．黄芪葛根配伍调节糖尿病大鼠血糖血脂炎症的作用与机制[J]．中国实验方剂学杂志，2018，24(11)：81-86．

秦阳，高颖，高英，等．桑白皮黄酮提取物对2型糖尿病大鼠非酒精性脂肪肝血管生成相关基因的影响[J]．中国实验方剂学杂志，2017，23(17)：144-148．

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Qidi Tangshen Prescription （QDTS） Regulate Akt1/HIF-1α/Bcl-xl Signaling Pathway to Improve Podocyte Autophagy in Diabetic Nephropathy

Treatment of Prostate Cancer by Targeting PI3K/Akt Signaling Pathway with Traditional Chinese Medicine： A Review

Chinese Medicine Regulates Hepatocellular Carcinoma-related Signaling Pathways： A Review

Effect of Modified Shengjiangsan on Renal Endoplasmic Reticulum Stress and Sirt1/PERK Pathway in Rat Model of Diabetic Nephropathy

Analysis of Potential Active Ingredients and Mechanism of Baihu Jia Renshentang in Treatment of Obesity Complicated with Type 2 Diabetes Mellitus

Related Author

GAO Fei

XIE Huidi

YU Borui

ZHOU Ying

SHI Yang

ZHANG Xianhui

LIU Hongfang

LI Shenglong

Related Institution

Beijing Chaoyang District Hospital of Traditional Chinese Medicine

Dongzhimen Hospital，Beijing University of Chinese Medicine

First Medical Center of Chinese PLA General Hospital

Beijing Puren Hospital

School of Traditional Chinese and Western Medicine， Gansu University of Chinese Medicine

Postal code：100700
Tel：010-84076882 Email：syfjx_2010@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备11006657号-10 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰