GSK2193874通过调控TRPV4表达改善肾结石小鼠肾纤维化的作用及机制  

Effects and mechanism of GSK2193874 on improving renal fibrosis in kidney stone mice by regulating TRPV4 expression

作　　者：宫宇 章静 巴正 高宇奎 田齐星 詹凤丽 卓栋 GONG Yu;ZHANG Jing;BA Zheng;GAO Yukui;TIAN Qixing;ZHAN Fengli;ZHUO Dong(Department of Urology,The First Affiliated Hospital of Wannan Medical College,Wuhu 241001,Anhui,China)

机构地区：[1]皖南医学院第一附属医院弋矶山医院泌尿外科,安徽芜湖241001 [2]皖南医学院第二附属医院泌尿外科,安徽芜湖241000

出　　处：《皖南医学院学报》2025年第1期16-19,共4页Journal of Wannan Medical College

基　　金：芜湖市科技计划项目(2022jc53)。

摘　　要：目的:探讨瞬时感受器电位香草素受体4(TRPV4)对肾结石小鼠肾纤维化进展的影响。方法:将小鼠分为对照组、模型组、药物干预组,模型组小鼠腹腔注射乙醛酸,药物干预组小鼠腹腔注射乙醛酸和GSK2193874。分别记录3组小鼠体质量变化,12 d后处死小鼠,ELISA检测小鼠血样中血清尿素氮(BUN)和血清肌酐(Scr)水平;HE染色观察小鼠肾脏病理的变化;Masson染色观察小鼠肾脏间质纤维化情况;Von Kossa染色观察小鼠肾脏钙盐沉积情况;Western blot检测小鼠肾脏组织中TRPV4、Col-Ⅰ和α-SMA蛋白的表达情况。结果:从第3天起模型组小鼠的体质量低于对照组和药物干预组小鼠(P<0.05);从第4天起药物干预组的小鼠体质量也低于对照组小鼠(P<0.05)。与对照组比较,模型组小鼠的Scr、BUN、肾脏损伤、胶原蛋白沉积、TRPV4、α-SMA和Col-Ⅰ蛋白的表达升高(P<0.05);与模型组比较,药物干预组的上述趋势得到逆转(P<0.05)。结论:GSK2193874可以抑制TRPV4表达,缓解肾结石小鼠肾纤维化的进程,保护肾功能。Objective:To investigate the effect of TRPV4 on the progression of renal fibrosis in mouse models with kidney stones.Methods:The mice were divided into control group,model group and drug intervention group.Except for the control group,mice in each group were intraperitoneally injected with glyoxylic acid,and those in the drug intervention group were intraperitoneally injected with GSK2193874.The changes of body weight of mice in three groups were recorded separately.Then the mice were sacrificed after 12 days.ELISA was used to detect blood urea nitrogen(BUN)and serum creatinine(Scr)levels in mouse blood samples.Pathological changes in mouse kidneys were observed through HE staining.Masson staining was performed to observe the renal interstitial fibrosis in mice.Calcium salt deposition in mouse kidneys was examined using Von Kossa staining.Western blot was used to detect the expression of TRPV4,Col-Ⅰ,andα-SMA proteins in the kidney tissue.Results:By the third day,the weight was significantly lower in the mice in model group than that in the control group and the drug intervention group(P<0.05).By the fourth day,the weight of mice in the drug intervention group was significantly lower than that of the control group(P<0.05).Compared with the control group,the expression levels of Scr,BUN,kidney injury,collagen deposition,TRPV4,α-SMA,and Col-Ⅰproteins in the model group were all increased(P<0.05).Compared with the model group,the above trends were reversed in the drug intervention group(P<0.05).Conclusion:GSK2193874 can inhibit TRPV4 expression,alleviate the process of renal fibrosis in mouse models with kidney stones,and protect kidney function.

关 键 词：肾纤维化 肾结石 瞬时感受器电位香草素受体4 GSK2193874 

分 类 号：R692[医药卫生—泌尿科学] R-332[医药卫生—外科学]