中国中医药信息杂志2024,Vol.31Issue(1):97-103,7.DOI:10.19879/j.cnki.1005-5304.202303038
葛根芩连汤对2型糖尿病db/db小鼠胰腺组织PERK/ATF4/CHOP信号通路的影响
Effects of Gegen Qinlian Decoction on PERK/ATF4/CHOP Signaling Pathway in Pancreatic Tissue of Mice with Type 2 Diabetes Mellitus
摘要
Abstract
Objective To observe the effects of Gegen Qinlian Decoction on pancreatic endoplasmic reticulum stress in mice with type 2 diabetes mellitus(T2DM);To explore its mechanism of action in the treatment of T2DM.Methods Totally 75 SPF male db/db mice were randomly divided into model group,metformin group,and Gegen Qinlian Decoction high-,medium-,low-dosage groups,with 15 mice in each group.15 db/m mice were set as the blank group.The administration groups received corresponding medicine for gavage for 12 weeks.Body mass,fasting blood glucose(FBG)and glycated hemoglobin(HbA1c)in mice were detected,HE staining was used to observe the pathological changes of pancreatic tissue,the apoptosis of islet cells was determined by TUNEL staining,Western blot was used to detect pancreatic tissue glucose regulatory protein 78(GRP78),protein kinase R-like endoplasmic reticulum kinase(PERK),p-PERK,activated transcription factor 4(ATF4)and C/EBP homologous protein(CHOP)protein expression,RT-PCR was used to detect pancreatic tissue PERK,ATF4,CHOP mRNA expressions.Results Compared with the blank group,the body mass,FBG and HbA1c contents in the model group significantly increased(P<0.01);the pancreatic tissue structure was incomplete,with blurry boundaries and vacuoles inside,leading to a significant increase in pancreatic islet cells apoptosis(P<0.01);the expressions of GRP78,p-PERK,ATF4,and CHOP proteins in pancreatic tissue significantly increased(P<0.01),and the mRNA expressions of PERK,ATF4 and CHOP significantly increased(P<0.01).Compared with the model group,the body mass,FBG and HbA1c contents of mice in each administration group significantly decreased(P<0.05,P<0.01);pathological changes in pancreatic tissue was reduced,and islet cells apoptosis decreased to varying degrees(P<0.05,P<0.01);the expressions of GRP78,p-PERK,ATF4 and CHOP proteins in pancreatic tissue significantly decreased(P<0.01)in Gegen Qinlian Decoction high-and medium-dosage groups and the metformin group,and the expressions of PERK,ATF4 and CHOP mRNA significantly decreased(P<0.05,P<0.01).Conclusion Gegen Qinlian Decoction may decreased pancreatic islet cells apoptosis,protect pancreatic cell function,and delay the progression of T2DM by inhibiting the endoplasmic reticulum stress PERK/ATF4/CHOP signaling pathway,and down-regulating the expressions of related genes and proteins.关键词
葛根芩连汤/2型糖尿病/内质网应激/PERK/ATF4/CHOP信号通路/小鼠Key words
Gegen Qinlian Decoction/type 2 diabetes mellitus/endoplasmic reticulum stress/PERK/ATF4/CHOP signaling pathway/mice分类
医药卫生引用本文复制引用
关晓文,梁永林,朱向东,苏菲,张媛媛,翟艳会..葛根芩连汤对2型糖尿病db/db小鼠胰腺组织PERK/ATF4/CHOP信号通路的影响[J].中国中医药信息杂志,2024,31(1):97-103,7.基金项目
甘肃省教育厅产业支撑计划(2021CYZC-03) (2021CYZC-03)
宁夏回族自治区重点研发计划(2022CMG02034) (2022CMG02034)
兰州市创新创业人才项目(2019-RC-100) (2019-RC-100)