南方医科大学学报2025，Vol.45Issue(12)：2585-2597,13.DOI:10.12122/j.issn.1673-4254.2025.12.06
参芪泄浊饮通过调控Rap1/MAPK/FoxO3a信号通路改善氧化应激及炎症反应延缓大鼠肾纤维化
Shenqi Xiezhuo Decoction alleviates renal fibrosis in rats by ameliorating oxidative stress and inflammation through the Rap1/MAPK/FoxO3a signaling pathway
摘要
Abstract
Objective To explore the mechanism of Shenqi Xiezhuo Decoction(SQXZD)for improving renal fibrosis(RF)in rats.Methods The chemical components of SQXZD were identified using UPLC-Q Exactive/MS,and component-disease target network and enrichment analyses were conducted to screen the key pathways and targets.In the animal experiment,49 male SD rats were randomized equally into blank control group,sham operation group,unilateral ureteral obstruction-induced RF model group,losartan treatment(daily dose 4.6 mg/kg)group,and low-,medium-,and high-dose SQXZD(9.7,19.4,and 38.8 g/kg,respectively)treatment groups.After 14 days'treatment,renal pathologies and collagen deposition of the rats were examined with HE and Masson staining,and serum levels of BUN,Cr,SOD,MDA,GSH-px,IL-6,and TNF-α were detected.Western blotting and qRT-PCR were used to detect renal protein and mRNA expressions of α-SMA,Col-I,NAKED2,Rap1,B-raf,Raf-1,MEK3/6,p38MAPK,MEK,ERK1/2,p-ERK1/2,FoxO3a,p-FoxO3a,and MnSOD.Results A total of 263 chemical components were identified in SQXZD.Network pharmacology revealed 170 intersecting targets between the components and RF enriched in the MAPK,Rap1,and FoxO pathways.The rat models of RF showed abnormal renal structural changes,increased fibrosis area,elevated serum BUN,Cr,MDA,IL-6,and TNF-α levels,reduced SOD and GSH-px levels,upregulated renal expressions of α-SMA,Col-I,NAKED2,Rap1,B-raf,MEK,ERK1/2,p-ERK1/2,MEK3/6,and p38MAPK,and downregulated Raf-1,FoxO3a,p-FoxO3a,and MnSOD expressions.Treatment with losartan and SQXZD(especially at the medium dose)obviously lessened renal pathologies,improved renal functions,alleviated oxidative stress and inflammation,and ameliorated abnormal changes in the Rap1/MAPK/FoxO3a signaling pathway in the rat models.Conclusion SQXZD alleviates RF and improves renal function in rats possibly by ameliorating renal oxidative stress and inflammation via regulating the Rap1/MAPK/FoxO3a signaling pathway.关键词
参芪泄浊饮/肾纤维化/氧化应激/炎症因子/Rap1/MAPK/FoxO3a信号通路Key words
Shenqi Xiezhuo Decoction/renal fibrosis/oxidative stress/inflammatory factors/Rap1/MAPK/FoxO3a signaling pathway引用本文复制引用
LU Xiaoyu,LIU Zhihui,LIU Ye,PANG Tianxiao,BIAN Rong,GUO Ling,HE Xuehong..参芪泄浊饮通过调控Rap1/MAPK/FoxO3a信号通路改善氧化应激及炎症反应延缓大鼠肾纤维化[J].南方医科大学学报,2025,45(12):2585-2597,13.基金项目
国家中医药管理局高水平中医药重点学科建设项目(zyyzdxk-2023033,zyyzdxk-2023036) （zyyzdxk-2023033,zyyzdxk-2023036）
辽宁省科学技术计划面上项目(2024-MS-124) （2024-MS-124）
2022年全国名老中医药专家传承工作室建设项目(国中医药人教函[2022]75号) （国中医药人教函[2022]75号）
