调控Hippo信号通路对间充质干细胞氧化应激耐受能力的影响

doi:10.3969/j.issn.1002-1949.2018.05.010

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摘要目的探讨调控Hippo信号通路对小鼠骨髓来源间充质干细胞(mMSCs)氧化应激耐受能力的影响。方法直接贴壁法分离 C57BL/6小鼠原代mMSCs，通过流式细胞学检测和诱导其成骨、成软骨、成脂分化进行鉴定，采用非接触共培养诱导其向ATⅡ细胞分化；通过2-脱氧-D-葡萄糖(2-DG)及XMU-MP-1调节Hippo信号通路，根据不同浓度的双氧水（H2O2）共培养来模拟氧化应激损伤。应用MTT法评估H2O2诱导氧化应激损伤对mMSCs存活的影响；Western blot法检测mMSCs中Hippo信号通路关键组分，评估H2O2诱导氧化应激损伤对Hippo信号通路的影响；同时应用Western blot法检测凋亡相关蛋白Bax及Bcl-2的表达，评估Hippo信号通路调控mMSCs氧化应激耐受能力的机制。结果 2-DG呈浓度依赖性的激活Hippo信号通路，而通过XMU-MP-1可抑制Hippo信号通路活化。H2O2能导致mMSCs损伤和抑制其Hippo信号通路的活性，凋亡相关蛋白Bcl-2/Bax表达比例下调是导致mMSCs损伤的可能机制；而活化Hippo信号通路能通过上调Bcl-2/Bax表达比例，增强mMSCs氧化应激耐受能力；通过抑制Hippo信号通路下调Bcl-2/Bax表达比例，减弱mMSCs氧化应激耐受和存活能力。结论 Hippo信号通路可通过调控凋亡相关蛋白Bcl-2/Bax表达比例，影响mMSCs的存活和氧化应激耐受能力。

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	董亮
	李朗
	惠姣洁
	高飞
	王秋卉
	杨岚
	张江茜
	严洁

关键词 ： Hippo信号通路, 间充质干细胞(mMSCs), 氧化应激耐受, 凋亡相关蛋白, Bcl-2/Bax

基金资助:国家自然科学基金(81400054)；江苏省自然科学基金(BK20140122)；江苏省青年医学重点人才项目(QNRC2017179)

通讯作者: 李朗(1983-)，女，硕士研究生，主治医师，E-mail:shininglang@163.com。

作者简介: 董亮(1982-)，男，博士，副主任医师，E-mail:dongliang@njmu.edu.cn。

引用本文:

董亮，李朗，惠姣洁，高飞，王秋卉，杨岚，张江茜，严洁. 调控Hippo信号通路对间充质干细胞氧化应激耐受能力的影响[J]. 中国急救医学, 2018, 38(5): 414-.
Dong Liang, Li Lang, Hui Jiao-jie, Gao Fei, Wang Qiu-hui, Yang Lan, Zhang Jiang-qian, Yan Jie. Effects of Hippo signaling on anti-oxidative stress of mesenchymal stem cells in vitro. Chinese Journal of Critical Care Medicine, 2018, 38(5): 414-.

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http://www.cnemergency.org.cn/CN/10.3969/j.issn.1002-1949.2018.05.010 或 http://www.cnemergency.org.cn/CN/Y2018/V38/I5/414

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