Effect of Coptidis Rhizoma on Endoplasmic Reticulum Stress Pathway PERK/ATF4/CHOP in Pancreas of Rats with Type 2 Diabetes Mellitus

Jie SHEN; Shan-shan ZHOU; Xiao-gang WAN

doi:10.13422/j.cnki.syfjx.20191641

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Effect of Coptidis Rhizoma on Endoplasmic Reticulum Stress Pathway PERK/ATF4/CHOP in Pancreas of Rats with Type 2 Diabetes Mellitus

Pharmacology | 更新时间：2021-02-09

- Effect of Coptidis Rhizoma on Endoplasmic Reticulum Stress Pathway PERK/ATF4/CHOP in Pancreas of Rats with Type 2 Diabetes Mellitus
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 16, Pages: 50-55(2019)
- 作者机构：
  
  1.广州中医药大学　第一附属医院，广州　 510405；
  2.湖北中医药大学，武汉　 430065
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191641
  CLC： R2-0; R289; R285.5; R587.1
- Received：21 February 2019，
  
  Published Online：08 May 2019，
  
  Published：20 August 2019
- 稿件说明：
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Jie SHEN, Shan-shan ZHOU, Xiao-gang WAN. Effect of Coptidis Rhizoma on Endoplasmic Reticulum Stress Pathway PERK/ATF4/CHOP in Pancreas of Rats with Type 2 Diabetes Mellitus[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(16): 50-55.
DOI：

Jie SHEN, Shan-shan ZHOU, Xiao-gang WAN. Effect of Coptidis Rhizoma on Endoplasmic Reticulum Stress Pathway PERK/ATF4/CHOP in Pancreas of Rats with Type 2 Diabetes Mellitus[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(16): 50-55. DOI： 10.13422/j.cnki.syfjx.20191641.

摘要

目的：

观察黄连对2型糖尿病大鼠的炎症因子、血糖、内质网应激信号通路蛋白激酶R样内质网激酶(PERK)/活化转录因子4(ATF4)/CCAAT/增强子结合蛋白同源蛋白(CHOP)相关蛋白的干预作用。

方法：

将80只雄性SPF级大鼠随机分为正常组、模型组、盐酸二甲双胍组、黄连组，每组20只。采用“10周高糖高脂饲料喂养＋经腹腔注入低剂量链脲佐菌素(STZ)”方案对非正常组大鼠造模。盐酸二甲双胍组予盐酸二甲双胍0.2 g·kg

－1

·d

－1

，黄连组按照剂量为0.4 g·kg

－1

·d

－1

给药，模型组、正常组大鼠均给予同等体积的蒸馏水，每天1次。待灌胃期终止，取血，酶联免疫吸附测定法(ELISA)检测各组大鼠的空腹血糖(FBG)，C反应蛋白(CRP)，肿瘤坏死因子-

(TNF-

)水平；采用免疫组化法检测各组大鼠胰腺组织葡萄糖调节蛋白78(GRP78)，CHOP，ATF4蛋白的表达；采用蛋白免疫印迹法(Western blot)检测各组大鼠胰腺组织PERK，磷酸化(p)-PERK蛋白的表达。

结果：

与正常组比较，模型组大鼠FBG，TNF-

，CRP水平及ATF4，CHOP，GRP78，p-PERK蛋白表达均明显升高(

0.05)；与模型组比较，黄连组和盐酸二甲双胍组FBG，TNF-

，CRP水平，ATF4，CHOP，GRP78，p-PERK蛋白表达均明显下降(

0.05)。

结论：

黄连能在一定程度上降低大鼠血糖，缓解炎性反应，可抑制质网应激PERK/ATF4/CHOP信号通道，减少CHOP，ATF4，GRP78，p-PERK的表达。

Abstract

Objective:

To observe the effect of Coptidis Rhizoma on blood sugar

inflammatory factors and protein kinase R-like endoplasmic reticulum kinase (PERK)/activating transcription factor 4(ATF4)/CCAAT/enhace-binding protein homologous protein (CHOP) pathway in type 2 diabetic mellitus rats.

Method:

The 80 SPF grade male rats were randomly divided into normal group

model group

metformin hydrochloride group

Coptidis Rhizoma group

with 20 rats in each group.The rats in the abnormal group were given " 10-week high-sugar and high-fat diet+ intraperitoneal injection of low dose streptozotocin (STZ)" regimen. Metformin hydrochloride group was given 0.2 g·kg

-1

·d

-1

while rhizoma coptidis group was given 0.4 g·kg

-1

·d

-1

. Both model group and normal group were given the same amount of distilled water once a day.Fasting blood glucose (FBG)

C reactive protein (CRP) and tumor necrosis factor-

(TNF-

) at an acute stage after 5-week intervention were determined by enzyme linked immunosorbent assay (ELISA) methods. Immunohistochemistry method was perforined with proteins glucoseregulated protein 78 (GRP78)

ATF4

CHOP.Western blot assay was used to detect PERK

phosphorylated PKR like endoplasmic reticulum regulating kinase(p-PERK).

Result:

Compared with normal group

the FBG

CRP

TNF-

p-PERK

GRP78

ATF4 and CHOP of model group improved(

0.05). The Coptidis Rhizoma group and positive control group could lower serum FBG

CRP

TNF-

p-PERK

GRP78

ATF4

CHOP in contrast with model group(

0.05).

Conclusion:

Coptidis Rhizoma can reduce blood sugar and reduce the levels of inflammatory factors

inhibit plasmic reticulum stress PERK/ATF4/CH0P pathway

and reduce CHOP

ATF4

GRP78

p-PERK expression in rats.

关键词

Keywords

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