南京医科大学学报（自然科学版）2025，Vol.45Issue(3)：311-318,8.DOI:10.7655/NYDXBNSN240954
线粒体靶向药物Mitochonic acid 5调控线粒体稳态减轻肾脏纤维化的机制研究
Mechanism research of mitochondria-targeted drug Mitochonic acid 5 regulating mitochondrial homeostasis to alleviate renal fibrosis
摘要
Abstract
Objective:To investigate the effect of mitochondrial targeting drug Mitochonic acid 5(MA-5)on renal fibrosis and its mechanism.Methods:Twenty-four 8-week-old SPF C57BL/6J male mice were randomly divided into four groups:control group,MA-5 group,unilateral ureteral obstruction(UUO)group,and UUO+MA-5 group.Mice in all four groups underwent surgery to expose the ureter and kidney.The UUO and UUO+MA-5 group received ureteral ligation,while the control and MA-5 groups had the ureter exposed and sutured without ligation.From the 2nd day after operation,the MA-5 and the UUO+MA-5 group received MA-5 by gavage continuously until the 7th day,whilethe control and UUO group were given the corresponding doses of corn oilby gavage.The mice were sacrificed on the 7th day after UUO,and the kidney and blood samples were collected.Subsequently,Masson and Sirius Red staining were used to assess renal fibrosis.The expression of α-smooth muscle actin(α-SMA)and Collagen Ⅰ(Col1)were explored by immunohistochemistry.Furthermore,Western blot was used to detect the expression of mitochondrial andaging-related proteins.Mouse renal tubular epithelial cells were cultured in vitro and stimulated with transforming growth factor-β(TGF-β).Western blot was used to detect the expression of α-SMA,Fibronectin,and Vimentin in tubular epithelial cells with or without MA-5 intervention.Results:Seven days after UUO,Masson and Sirius Red staining of renal tissue showed that the UUO group had severe renal fibrosis,and the UUO+MA-5 group had significantly reduced renal fibrosis compared to the UUO group.The results of Western Blot and immunohistochemistry showed that the expression of α-SMA and Col1 in the UUO+MA-5 group was significantly lower than that in the UUO group(P<0.05).Further study showed that mitochondrial biosynthesis,fusion and motility were decreased in the UUO group,with decreased expression of superoxide dismutase 2(SOD2).MA-5 treatment significantly increased the expression of Mitofilin in the kidney of UUO mice,improved mitochondrial function,and increased the expression of peroxisome-proliferator-activated receptor γ coactivator 1-α(PGC1-α),Mitofusin 2(Mfn2),the mitochondrial Rho GTPase 1(Miro1)and SOD2(all P<0.05).The results in vitro showed that MA-5 could reduce the expression of fibrosis-related proteins induced by TGF-β in cultured tubular epithelial cells(P<0.05).Conclusion:Renal fibrosis occurs in mice after UUO,and MA-5 can attenuate TGF-β induced tubular epithelial cells fibrosis by maintaining mitochondrial homeostasis.关键词
肾脏纤维化/线粒体/MA-5Key words
renal fibrosis/mitochondria/MA-5分类
临床医学引用本文复制引用
钱力,陈晨,李青,吴琳,邢昌赢,毛慧娟,袁杨刚..线粒体靶向药物Mitochonic acid 5调控线粒体稳态减轻肾脏纤维化的机制研究[J].南京医科大学学报（自然科学版）,2025,45(3):311-318,8.基金项目
国家自然科学基金(82170699,81870469,81670628) （82170699,81870469,81670628）
