miR-195抑制剂降低1型糖尿病小鼠肝脏氧化应激损伤

基础医学与临床 ›› 2020, Vol. 40 ›› Issue (6): 811-816.

miR-195抑制剂降低1型糖尿病小鼠肝脏氧化应激损伤

胡苏琴, 王圣凯, 吴杭菲, 郑靖宇, 李剑敏^*

温州医科大学附属第一医院病理科, 浙江温州 325015

收稿日期:2019-12-09 修回日期:2020-03-21 出版日期:2020-06-05 发布日期:2020-05-29
通讯作者: *wzyxyljmin@163.com
基金资助:
浙江省自然科学基金(LY14H020005)

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

HU Su-qin, WANG Sheng-kai, WU Hang-fei, ZHENG Jing-yu, LI Jian-min^*

Department of Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China

Received:2019-12-09 Revised:2020-03-21 Online:2020-06-05 Published:2020-05-29
Contact: *wzyxyljmin@163.com

摘要/Abstract

摘要： 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活力均显著下降(P＜0.05);与DM 组相比,DM+antago 组miR-195mRNA的表达,MDA含量及AcFoxo1/Foxo1 蛋白表达明显下降(P＜0.05),而Sirt1、Foxo1 mRNA及蛋白表达,T-SOD活力均明显升高(P＜0.05)。结论 miR-195在1型糖尿病大鼠肝脏氧化应激中表达增加,Sirt1可能是miR-195的作用靶点。

关键词: 1型糖尿病, miR-195, Sirt1, 氧化应激, 凋亡

Abstract: 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 C57BL/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 the DM 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.

Key words: type 1 diabetes, miR-195, silent information regulator 1, oxidative stress, apoptosis

中图分类号:

R587.1

胡苏琴, 王圣凯, 吴杭菲, 郑靖宇, 李剑敏. miR-195抑制剂降低1型糖尿病小鼠肝脏氧化应激损伤[J]. 基础医学与临床, 2020, 40(6): 811-816.

HU Su-qin, WANG Sheng-kai, WU Hang-fei, ZHENG Jing-yu, LI Jian-min. miR-195 inhibitor reduces liver oxidative stress injury in type 1 diabetic mice[J]. Basic & Clinical Medicine, 2020, 40(6): 811-816.

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