期刊导航

论文摘要

三甲氧苄嗪对脂肪来源间充质干细胞氧化应激损伤的影响及机制研究

The Mechanisms of Trimetazidine Alleviating the Oxidative Stress in Adipose-derived Mesenchymal Stem Cells

作者:唐茂涵, 张艳杰, 刘银等

Author:TANG Mao-han, ZHANG Yan-jie, LIU Yin. et al

收稿日期:          年卷(期)页码:2017,48(2):173-178

期刊名称:四川大学学报(医学版)

Journal Name:JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION)

关键字:脂肪来源间充质干细胞 氧化应激 细胞凋亡 三甲氧苄嗪 线粒体

Key words:Adipose-derived mesenchymal stem cells Oxidative stress Apoptosis Trimetazidine Mitochondrial

基金项目:

中文摘要

【摘要】 目的 研究三甲氧苄嗪(TMZ)对脂肪来源间充质干细胞(ADSCs)氧化应激凋亡的影响及其机制。 方法 使用双酶消化获得SD大鼠脂肪组织的ADSCs,进行流式细胞学鉴定和多向分化潜能评估;应用过氧化氢(H2O2)诱导的ADSCs损伤凋亡模型,使用不同浓度的TMZ(250 μmol/L、500 μmol/L)干预氧化应激损伤的过程;Hoechst 33342染色定性分析凋亡细胞形态;JC-1线粒体膜电位染色和线粒体电镜检测观察TMZ作用下线粒体损伤逆转情况;Western blot检测TMZ对线粒体凋亡通路蛋白的影响;通过检测活性氧簇(ROS)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、丙二醛(MDA)水平评价TMZ对ADSCs抗氧化能力的作用。结果 获取的ADSCs,阳性表达CD29和CD90抗原,低或不表达CD34、CD45及CD31;ADSCs能够成功被诱导分化为脂肪细胞和骨性细胞;H2O2处理ADSCs,细胞凋亡数量增加,线粒体膜电位降低,线粒体结构破坏崩解,保护性凋亡蛋白(Bc12)表达下降,凋亡蛋白(Bax、Bad、Caspase3)表达上调;胞内ROS含量与MDA的质量摩尔浓度上升,SOD的活性和GSH的质量摩尔浓度降低。TMZ对ADSCs有浓度依赖性的保护作用,可降低H2O2诱导的细胞凋亡,逆转线粒体低电位,减轻H2O2对线粒体结构的损伤,提高Bc12的表达和下调Bax、Bad及Caspase3的表达,减低过量的ROS和 MDA,恢复SOD和GSH的抗氧化系统功能。结论 TMZ通过调控保护性蛋白的表达和提高内源性抗氧化能力,提高ADSCs 的存活率,从而逆转氧化应激损伤。

英文摘要

【Abstract】 Objective To investigate the effects of trimetazidine (TMZ) on the oxidative stress injury in adipose-derived mesenchymal stem cells (ADSCs). Methods ADSCs derived from adipose tissue of SD rats were characterized by flow cytometry and multiline age differentiation. ADSCs apoptosis was induced by H2O2 in vitro , Dirrerent concentration of TMZ (250 μmol/L, 500 μmol/L) was used to protect ADSCs from apoptosis. The morphological features of apoptotic ADSCs were analyzed by Hoechst 33342, mitochondrial potential and structure was analyzed by JC-1 staining and electron microscope, respectively. The apoptotic proteins were detected by Western blot. The effect of TMZ on antioxidant capacity of ADSCs was evaluated by detecting reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA). Results The isolated ADSCs expressed high levels of CD29 and CD90, low levels of CD34 and CD45 and no expression of CD31. ADSCs could be induced to adipocyte and osteoplastic cells. After being treated by H2O2, ADSCs displayed apoptosis characteristics with increased number of apoptotic cells, decreased mitochondrial transmembrane potential and damaged mitochondria. The expressions of apoptotic proteins, including Bax, Bad, and Caspase3, were dramatically increased compared to the controls; however, the anti-apoptotic protein Bcl2 was decreased. At the meantime, the contents of ROS and MDA were elevated, but the concentrations of SOD and GSH were reduced. The treatment of TMZ could partly reverse above negative impacts to ADSCs. Conclusion TMZ could improve the survival rate of ADSCs by enhancing anti-oxidant defense systems to remove excessive ROS and regulating the expression of protective protein.

关闭

Copyright © 2020四川大学期刊社 版权所有.

地址:成都市一环路南一段24号

邮编:610065