基于内质网应激探讨葛根芩连汤对非酒精性脂肪肝大鼠PERK-eIF2α通路的影响  

Effects of Gegen Qinlian Decoction on PERK-eIF2α pathway in rats with nonalcoholic steatohepatitis based on endoplasmic reticulum stress

作　　者：张超云[1] 费娜 郝鹏飞[1] 高丽[1] 庞国明 ZHANG Chaoyun;FEI Na;HAO Pengfei;GAO Li;PANG Guoming(Nanyang Institute of Technology,Henan Key Laboratory of Zhang Zhongjing Formulae and Herbs for Immunoregulation,Henan Nanyang 473000,China;HenanTechnician College of Medicine and Health,Henan Kaifeng 475000,China;Kaifeng Hospital of Traditional Chinese Medicine,Kaifeng 475001,Henan Kaifeng 475001,China)

机构地区：[1]南阳理工学院河南省张仲景方药与免疫调节重点实验室,河南南阳473000 [2]河南医药健康技师学院,河南开封475000 [3]开封市中医院,河南开封475001

出　　处：《中国医院药学杂志》2024年第4期384-390,共7页Chinese Journal of Hospital Pharmacy

基　　金：河南省科技攻关项目(编号:212102311102)。

摘　　要：目的:考察葛根芩连汤(GQD)对非酒精性脂肪肝(nonalcoholic fatty liver disease,NAFLD)大鼠模型治疗作用及对PERK-eIF2α通路的影响,探讨葛根芩连汤对该模型大鼠内质网应激(endoplasmic reticulum stress,ERS)的作用机制。方法:采用高脂高果糖饲料建立非酒精性脂肪肝大鼠模型,分别设置空白组、模型组、阳性组以及不同剂量给药组,检测各组大鼠体态、ALT、AST、TG、TC、胰岛素抵抗指数和胰岛素敏感指数,以考察GQD治疗NAFLD大鼠的效果;再通过CO-IP、Western blot和RT-qPCR实验考察GQD对NAFLD模型大鼠PERK-eIF2α通路的影响,评价GQD对NAFLD模型大鼠内质网应激反应的作用。结果:各剂量的GQD均可缓解NAFLD模型大鼠的体质量反常下降,均可降低NAFLD模型大鼠ALT、AST、TG、TC,缓解NAFLD所致肝功能受损及脂质代谢紊乱,提升NAFLD大鼠的胰岛素敏感指数,降低其胰岛素抵抗指数,且治疗效果均呈现良好的剂量依赖性。CO-IP、Western blot和RT-qPCR检测结果则提示,NAFLD大鼠模型在经过GQD的治疗后,其肝组织中GRP78&PERK复合物量显著提升,eIF2α、P-eIF2α、ATF4、CHOP等蛋白及mRNA表达量均得到抑制,而GADD34蛋白及mRNA表达量得到提升,以上结果也呈现较好的剂量依赖性。结论:葛根芩连汤可通过调控PERK-eIF2α-ATF4信号通路对非酒精性脂肪肝大鼠肝脏的内质网应激反应有一定缓解作用。Objective To evaluate the therapeutic effect of Gegen Qinlian Decoction(GQD)on rat model with Nonalcoholic Fatty Liver Disease(NAFLD)and its effect on PERK-eIF2αpathway,investigating the mechanism of GQD's action on Endoplasmic Reticulum Stress(ERS).Methods The non-alcoholic fatty liver rat model was induced using high-fat and high-fructose diet.A control group,a model group,a positive group and different dosage groups were set up.Physical appearance,ALT,AST,TG,TC,insulin resistance index and insulin sensitivity index were measured to assess the efficacy of GQD on NAFLD rats.CO-IP,Western blot and RT-qPCR experiments were conducted to investigate the impact of GQD on the PERK-eIF2αpathway in NAFLD rats,and evaluate its role in the endoplasmic reticulum stress response.Results Each GQD dosage could alleviate abnormal body weight decline in NAFLD rats,and significantly reduce the ALT,AST,TG,TC levels.It mitigated the damage of liver function and lipid metabolism disorders caused by NAFLD,increased the insulin sensitivity index,and reduced the insulin resistance index,with therapeutic effects showing dose-dependency.CO-IP,Western blot and RT-qPCR test results indicated that,after GQD treatment,there was a significant increase in the amount of GRP78&PERK complex in the liver tissues,suppression of eIF2α,P-eIF2α,ATF4,CHOP and other proteins and mRNA,and an increase in GADD34 protein and mRNA expression,with all effects exhibiting dose-dependency.Conclusion Gegen Qinlian Decoction can alleviate the endoplasmic reticulum stress response in the liver of NAFLD rats by regulating the PERK-eIF2α-ATF4 signaling pathway.

关 键 词：葛根芩连汤 非酒精性脂肪肝 内质网应激 G蛋白偶联受体78 蛋白激酶R样内质网激酶 

分 类 号：R285[医药卫生—中药学]