中医药信息2025，Vol.42Issue(6)：18-27,10.DOI:10.19656/j.cnki.1002-2406.20250604
基于ERK1/2信号通路探讨怡肾丸对单侧输尿管梗阻大鼠线粒体氧化应激的影响
Effects of Yishen Pill on Mitochondrial Oxidative Stress in Unilateral Ureteral Obstruction Rats Based on the ERK1/2 Signaling Pathway
摘要
Abstract
Objective:To investigate the mechanism by which Yishen Pill mediates the ERK1/2 signaling pathway through mitochondrial oxidative stress to reduce cell apoptosis and delay renal interstitial fibrosis.Methods:Sixty-four male SD rats were randomly divided into the sham operation group(16 rats)and the operation group(48 rats)according to a random number table.The operation group was established with a unilateral ureteral obstruction model.On the day of modeling,the rats were further divided into the model group,Yishen Pill group,and enalapril group.The Yishen Pill group was treated with 1.62 g/(kg·d)of Yishen Pill solution via oral gavage,and the enalapril group was treated with 1.05 mg/(kg·d)enalapril solution via oral gavage.The remaining groups were given the same volume of distilled water.After successful modeling,rats were sacrificed on days 3,7,and 21,and the kidneys were removed.ROS levels were detected by DCFH-DA staining,and the expression of ERK1/2-mediated mitochondrial apoptosis-related proteins in the kidney was detected by immunohistochemistry.Hematoxylin and eosin(HE)staining and Masson staining were used to observe the histopathological changes in the kidney tissues.Results:Compared to the sham operation group,the rats in the operation group showed hair loss,and the kidneys showed noticeable enlargement and cortical thinning on day 3 post-surgery.The treatment groups exhibited smaller kidney sizes compared to the model group.No significant pathological changes or structural damage were observed in the kidney tissues of the sham operation group.In the model group,different degrees of tubular epithelial cell injury,atrophy,interstitial fibrosis,inflammatory cell infiltration,sparse capillaries,and collagen deposition were observed.Mitochondrial structural damage was also noted,while these conditions were alleviated in the Yishen Pill and enalapril groups.Compared to the sham operation group,the model group showed a significant decrease in the expression of the mitochondrial apoptosis-related protein Bcl-2(P<0.01),while the expression of ERK1/2,phosphorylated ERK1/2(p-ERK1/2),Bax,and Cyt C increased significantly(P<0.01).Compared to the model group,rats in the Yishen Pill and enalapril groups showed a decrease in tubular epithelial cell apoptosis and reduced expression of ERK1/2,p-ERK1/2,Bax,and Cyt C(P<0.01),with an increase in Bcl-2 expression(P<0.01).Conclusion:Yishen Pill alleviates renal interstitial fibrosis by regulating the expression of mitochondrial apoptosis-related proteins through the oxidative stress-mediated ERK1/2 signaling pathway,thus mitigating chronic renal failure.关键词
怡肾丸/肾间质纤维化/氧化应激/ERK1/2/细胞凋亡Key words
Yishen Pill/Renal interstitial fibrosis/Oxidative stress/ERK1/2/Cell apoptosis引用本文复制引用
陈珂,何泽云,彭亚平,李旭华..基于ERK1/2信号通路探讨怡肾丸对单侧输尿管梗阻大鼠线粒体氧化应激的影响[J].中医药信息,2025,42(6):18-27,10.基金项目
湖南省自然科学基金项目(2021JJ30522) （2021JJ30522）
湖南省中医药科研计划项目(D2022209) （D2022209）
湖南中医药大学校级科研基金项目(2018XJJJ35) （2018XJJJ35）
