线粒体靶向治疗对轻度肾积水灌注损伤的保护作用研究

Effect of mitochondrial targeted therapy in protective of mild hydronephrosis renal experiencing perfusion injury

目的 观察线粒体靶向治疗对轻度肾积水灌注损伤的保护作用。方法 取24只新西兰大白兔,分别建立轻度积水肾模型,再随机分为4个亚组(M1组、M1′组、M2组、M2′组),每组6只。经B超检查造模成功后,M1′组和M2′组分别行环孢素A(CsA)灌胃1周,1次/日。1周后,M1组和M1′组行60mmHg压力灌注;M2组和M2′组行100mmHg压力灌注。取肾组织行HE染色,光镜下观察肾组织病理性改变,分别用免疫组织化学法和蛋白免疫印迹实验(Westernblot)检测细胞色素C(CytC)和凋亡诱导因子(AIF)表达,JC-1染色检测细胞膜电位的改变。结果 M1′组Paller氏评分[(15.0±2.3)分]低于M1组[(26.0±4.2)分],差异有统计学意义(P<0.05)。M2′组Paller氏评分[(18.0±3.2)分]低于M2组[(37.0±3.1)分],差异有统计学意义(P<0.05)。与M1、M2组比较,M1′组和M2′组的CytC和AIF表达显著减少,差异均有统计学意义(P<0.05)。与M1、M2组比较,M1′组和M2′组治疗后肾小管细胞线粒体膜电位明显增加,组间比较差异有统计学意义(P<0.05)。结论 CsA可通过线粒体途径抑制细胞凋亡,从而减轻肾盂灌注时的损伤。

Objective To investigate renal protective effects of mitochondrial permeability hole inhibitor in treatment of renal based on rabbit models experiencing different degrees of hydronephrosis. Methods A total of 24 rabbits underwent a surgical procedure inducing mild hydronephrosis.Then the rabbits were randomly allocated into 4 subgroups (M1 group,M2 group,M1′ group,M2′ group) and 6 rabbits in each group.By B ultrasonic examination,the rabbits were all insured the success of the molding.And M1′ group and M2′ group were given Cyclosporin A (CsA) for one week,once a day.After one week,M1 group and M1′ group was perfused with 60 mm Hg fluid,and M2 group and M2′ group was perfused with 100 mm Hg fluid.Kidney pathological changes were examined by HE staining.Immunohistochemistry and Western blot were used to detect the expression of Cytochrome C (CytC) and apoptosis-inducing factor (AIF),and JC-1 staining was used to detect the mitochondrial membrane potential (MMP). Results Paller score of M1′ group (15.0±2.3) was significantly lower than that of M1 group (26.0±4.2)( P <0.05).And the Paller score of M2′ group (18.0±3.2) was significantly lower than that of M2 group (37.0±3.1)( P <0.05).The expression of CytC and AIF of M1′ group and M2′ group were significantly lower than that of M1 group and M2 group ( P <0.05).MMP of M1′ group and M2′ group were significantly higher than that of M1 group and M2 group ( P <0.05). Conclusion By mitochondrial targeted therapy,CsA could inhibit apoptosis,thus,it could alleviate the hydronephrosis.