血管紧张素Ⅱ预处理提高骨髓间充质干细胞抗凋亡能力  

AngiotensinⅡ preconditioning prevents mesenchymal stem cells from apoptosis

作　　者：宋奕辰[1] 胡亮[1] 周露[1] 范越[1] 黄松花 施睿臻[1] 李庆平[1] 

机构地区：[1]南京医科大学药理学系,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2014年第9期1157-1162,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金项目(30973534;81173052);南京医科大学科技发展基金(2013NJMU004)

摘　　要：目的:研究血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)预处理是否能提高骨髓间充质干细胞(mesenchymal stem cells,MSCs)的抗凋亡能力,探讨AngⅡ对MSCs预适应保护作用的可能机制。方法:用AngⅡ预处理大鼠MSCs细胞,采用H2O2或缺氧联合无血清(hypoxia and serum deprivation,Hypoxia/SD)的方法诱导细胞凋亡。用乳酸脱氢酶(lactate dehyarogenase,LDH)检测法、四唑盐比色法(MTT)和Hoechst 33342染色测定细胞活力和凋亡率;用Annexin V-FITC法定量检测细胞凋亡率;对MSCs进行罗丹明-123染色,用流式细胞术检测线粒体跨膜电位。结果:AngⅡ预处理MSCs能够明显减轻H2O2或Hypoxia/SD诱导的细胞损伤,显著提高细胞活力;逆转由Hypoxia/SD引起的线粒体跨膜电位的降低;ERK1/2阻断剂U0126和Akt阻断剂LY294002都能明显减弱AngⅡ对MSCs的预适应保护作用,增加细胞凋亡率。结论:AngⅡ对MSCs具有预适应保护作用,且主要通过Akt、ERK1/2途径发挥其抗凋亡能力。Objective：To examine whether Ang Ⅱ preconditioning improves the anti-apoptotic ability of bone marrow mesenchymal stem cells （MSCs）,and if so,what is its possible mechanism. Methods：MSCs cells from rats were pretreated with Ang Ⅱ, and apoptosis of MSCs was induced by H202 or hypoxia combined serum deprivation（Hypoxia/SD） method. Cell viability and apoptotic proportion were detected by lactate dehyarogenase （LDH） release, methye thiazolye telrazlium（MTT） assays and Hoechst 33342 staining. Annexin V-FITC assay was performed for quantification of apoptosis rate. The mitochondrial transmembrane potentia（△ψm） was detected by a flow cytometer using △ψm specific stain Rhodamine 123. Results：Ang Ⅱ preconditioning significantly reduced H2O2- or Hypoxia/SD-induced cell damage,increased cell viability,reversed Hypoxia/SD-induced mitochondrial membrane potential reduction. Both of ERK1/2 inhibitor U0126 and Akt inhibitor LY294002 significantly attenuated the the protective effects of Ang Ⅱ preconditioning on the viability and apoptosis rate of MSCs. Conclusion： Ang Ⅱ preconditioning prevents MSCs from apoptosis, and Akt and ERK1/2 signalling pathway may be implicated in the effect of Ang Ⅱ.

关 键 词：骨髓间充质干细胞 血管紧张素Ⅱ 预适应 氧化应激 凋亡 

分 类 号：Q255[生物学—细胞生物学]