中药新药与临床药理2025，Vol.36Issue(9)：1432-1440,9.DOI:10.19378/j.issn.1003-9783.2025.09.003
熊果酸对顺铂致肾毒性小鼠的保护作用及机制
Protective Effects and Mechanisms of Ursolic Acid Against Cisplatin-Induced Nephrotoxicity in Mice
摘要
Abstract
Objective To investigate the protective effects of ursolic acid against cisplatin-induced nephrotoxicity in mice based on its anti-inflammatory and antioxidant mechanisms.Methods Thirty male C57BL/6 mice were randomly divided into six groups(n=5 per group):normal control group,model group,low-dose ursolic acid treatment group(50 mg·kg-1),high-dose ursolic acid treatment group(100 mg·kg-1),dexamethasone treatment group(4 mg·kg-1),and ursolic acid monotherapy group(100 mg·kg-1).The low-and high-dose ursolic acid groups and the dexamethasone group received daily treatments for 4 consecutive.Ursolic acid was administered via oral gavage(5 mL·kg-1),while dexamethasone was administered via intraperitoneal injection.The normal control group and model group received an equivalent volume of 0.5%CMC-Na solution via oral gavage.Except for the control and ursolic acid monotherapy groups,all other groups were intraperitoneally injected with cisplatin(15 mg·kg-1)on the second day of the treatment period to establish a renal injury model.The kidney index was calculated,and biochemical analyses were performed.Renal function markers:serum uric acid(UA),blood urea nitrogen(BUN),and serum creatinine(Scr)levels;Oxidative stress markers:serum glutathione(GSH)levels,renal malondialdehyde(MDA)content,and superoxide dismutase(SOD)activity;Renal tissue TNF-α levels were measured by ELISA.Western Blot was used to determine the expression ratios of p-STAT3/STAT3,p-NF-κB p65/NF-κB p65,and p-p38 MAPK/p38 MAPK in renal tissues.Renal histopathological changes were assessed via hematoxylin and eosin(HE)staining.Results Compared with the normal control group,the model group exhibited a significantly increased kidney index(P＜0.05),elevated glomerular and tubular injury scores(P＜0.001),and markedly higher serum BUN,Scr,and UA levels(P＜0.05,P＜0.001).Additionally,serum GSH levels and renal SOD activity were significantly reduced(P＜0.05,P＜0.01),while renal MDA content was notably increased(P＜0.001).Renal TNF-α levels and the expression ratios of p-STAT3/STAT3,p-NF-κB p65/NF-κB p65,and p-p38 MAPK/p38 MAPK were all significantly elevated(P＜0.01,P＜0.001).Compared with the model group,the high-dose ursolic acid and Dexamethasone treatment groups showed significantly reduced kidney indices(P＜0.05).Both low-and high-dose ursolic acid treatment groups exhibited significantly lower glomerular and tubular injury scores(P＜0.05,P＜0.001),decreased serum BUN,Scr,and UA levels(P＜0.05,P＜0.01,P＜0.001),elevated serum GSH levels and renal SOD activity(P＜0.05,P＜0.01,P＜0.001),and reduced renal MDA content(P＜0.001).Furthermore,renal TNF-α levels and the expression ratios of p-STAT3/STAT3 and p-NF-κB p65/NF-κB p65 were significantly decreased(P＜0.05,P＜0.01,P＜0.001).The high-dose ursolic acid group also demonstrated a significant reduction in the p-p38 MAPK/p38 MAPK expression ratio(P＜0.01).Conclusion Ursolic acid effectively alleviates cisplatin-induced nephrotoxicity and improves renal histopathological damage,likely through suppression of acute renal inflammation and oxidative stress.关键词
熊果酸/顺铂/肾毒性/抗炎/抗氧化/小鼠Key words
ursolic acid/cisplatin/nephrotoxicity/anti-inflammatory/antioxidant/mice分类
医药卫生引用本文复制引用
彭冬玲,冯子健,刘永强,幸尚平..熊果酸对顺铂致肾毒性小鼠的保护作用及机制[J].中药新药与临床药理,2025,36(9):1432-1440,9.基金项目
广东省科技厅基础与应用基础研究基金项目(2022A1515011881) （2022A1515011881）
广西青苗人才项目(DC2400003575). （DC2400003575）
