天津中医药2024，Vol.41Issue(5)：642-648,7.DOI:10.11656/j.issn.1672-1519.2024.05.17
基于IRE1/GPR78信号通路研究三黄益肾胶囊抑制DKD大鼠肾组织细胞凋亡的作用机制
Study on the mechanism of Sanhuang Yishen Capsule in inhibiting apoptosis of renal tissue cells in DKD rats based on IRE1/GPR78 signaling pathway
摘要
Abstract
[Objective]To investigate the therapeutic effect of Sanhuang Yishen Capsule on diabetic kidney disease(DKD)model rats,and to study the effect of Sanhuang Yishen Capsule on IRE1/GPR78 signaling pathway in DKD model rats.[Methods]The 30 rats were divided into the normal group,model group,positive drug group,Sanhuang Yishen low dose group,and Sanhuang Yishen high dose group,6 rats in each group.Except for the normal group,the DKD model was established by a high-sugar and high-fat diet combined with streptozotocin(STZ)injection in the other groups.After modeling,the normal group and the model group were given normal saline every day,the positive drug group was given irbesartan 11.51 mg/kg every day,and Sanhuang Yishen low dose and Sanhuang Yishen high dose groups were given Sanhuang Yishen Capsule 0.81 g/kg and 1.62 g/kg respectively every day for 4 weeks.The therapeutic effect of Sanhuang Yishen Capsule on DKD was evaluated by observing the blood glucose and body weight levels of rats in each group during administration,detecting the levels of biochemical indicators,and renal histopathological staining after administration.Secondly,the effects of Sanhuang Yishen Capsule on oxidative stress and inflammatory factors in renal tissue of DKD rats were studied by kit and ELISA.Finally,the effects of Sanhuang Yishen Capsule on renal cell apoptosis and IRE1/GPR78 signaling pathway in DKD rats were studied by immunofluorescence,Tunel staining,and Western blot.[Results]After the intervention of Sanhuang Yishen Capsule,the body weight of DKD rats increased significantly,the blood glucose level decreased,the levels of serum creatinine(Cr),urea nitrogen(BUN)and 24-hour urine protein decreased,and the pathological changes of renal tissue in DKD rats were improved.The infiltration of inflammatory cells and fibrosis in renal tissue were reduced.In addition,Sanhuang Yishen Capsule can significantly increase the activity of SOD and GSH-Px in renal tissue of DKD model rats,reduce the level of MDA,and reduce the levels of IL-6,IL-1β,and TNF-α in the serum of DKD rats.Western blot results showed that Sanhuang Yishen Capsule significantly reduced the protein expression levels of endoplasmic reticulum stress marker factors GRP78 and IRE1 in renal tissue of DKD model rats,and effectively reduced the expression of pro-apoptotic proteins Bax,Caspase-3,and Caspase-9 in renal tissue of model rats,and increased the expression of anti-apoptotic protein BCL2.[Conclusion]Sanhuang Yishen Capsule has a significant therapeutic effect on DKD model rats,and its mechanism may be related to inhibiting the activation of the IRE1/GPR78 signaling pathway in renal tissue and improving endoplasmic reticulum stress.关键词
三黄益肾胶囊/糖尿病肾病/内质网应激/细胞凋亡/IRE1/GPR78信号通路Key words
Sanhuang Yishen Capsule/diabetic kidney disease/endoplasmic reticulum stress/apoptosis/IRE1/GPR78 signaling pathway分类
医药卫生引用本文复制引用
张辉,吕树泉,潘保朝..基于IRE1/GPR78信号通路研究三黄益肾胶囊抑制DKD大鼠肾组织细胞凋亡的作用机制[J].天津中医药,2024,41(5):642-648,7.基金项目
河北省中医药管理局科研计划项目(2021311).苏秀海全国名老中医药专家传承工作室(国中医药人教函[2022]75号). （2021311）
