miR-195抑制剂降低1型糖尿病小鼠肝脏氧化应激损伤

目的探究miR-195对1型糖尿病C57BL/6小鼠肝脏的Sirt1及其下游氧化应激和线粒体凋亡相关蛋白表达的影响。方法将小鼠分为对照组(Control组)、糖尿病组(DM组)、miR-195抑制剂组(DM+antago组)。按常规法复制DM组模型,miR-195抑制剂(2.5 mg/kg)转染DM+antago组小鼠。DM组及对照组只注射scrambled shRNA(2.5 mg/kg)作为对照。每周观察记录小鼠的体质量和血糖的增减情况。取新鲜的肝脏组织,一部分处理后制片并HE染色进行组织病理学观察;另一部分用于测定肝脏组织中MDA含量及T-SOD活力,并通过RT-qPCR和Western blot检测3组小鼠肝组织中相关指标的mRNA及蛋白含量。结果 1)与对照组相比,DM组肝脏组织的小叶都表现出结构紊乱,肝细胞明显水肿,胞质疏松;与糖尿病组相比,DM+antago组肝细胞水肿情况有所减轻。2)与对照组相比,DM组miR-195mRNA的表达,MDA含量及AcFoxo1/Foxo1蛋白表达均明显升高(P<0.05),而Sirt1、Foxo1 mRNA及蛋白表达,T-SOD活...

miR-195 inhibitor reduces liver oxidative stress injury in type 1 diabetic mice

Objective To investigate the effects of miR-195 on the expression of Sirt1 and its downstream oxidative stress and mitochondrial apoptosis-related proteins in the liver of type 1 diabetic C57 BL/6 mice.Methods Mice were divided into control group(Control group),diabetes group(DM group),and miR-195 inhibitor group(DM+antago group).The DM group model was replicated according to the conventional method,and miR-195 inhibitor(2.5 mg/kg)was transfected into DM+antago group mice.The DM group and the control group were injected with scrambled shRNA(2.5 mg/kg)only as a control.Observe and record the increase and decrease of body weight and blood glucose of mice every week.Take fresh liver tissue,one part is processed and made by HE staining for histopathological observation;the part is used to determine the MDA content and T-SOD activity in liver tissue.RT-qPCR and Western blot were used to detect the mRNA and protein content of related indicators in the liver tissue of the three groups of mice.Results 1)Compared with the control group,the leaflets of the liver tissue in theDM group showed structural disorders,hepatocytes were significantly edema,and the cytoplasm was loose;compared with the DM group,the hematocyte edema in the DM+antago group was reduced.2)Compared with the control group,miR-195 mRNA expression,MDA content and AcFoxo1/Foxo1 protein expression in the DM group were significantly increased(P<0.05),while Sirt1,Foxo1 mRNA and protein expression,and T-SOD activity were significantly reduced(P<0.05);Compared with the DM group,miR-195 mRNA expression,MDA content and AcFoxo1/Foxo1 protein expression in the DM+antago group decreased significantly(P<0.05),while Sirt1,Foxo1 mRNA and protein expression,and T-SOD activity were all Significantly increased(P<0.05).Conclusions The expression of miR-195 is increased in liver oxidative stress in type 1 diabetic rats.Sirt1 seems to be potential target of miR-195.