关键词XCT790;骨髓间充质干细胞;雌激素相关受体α;凋亡.DOC

XCT790对缺氧、无血清及高糖诱导MSCs凋亡的影响 杨光昕，陆德宾，江晓燕，赵 婕，陈 兵 （400038 重庆市 沙坪坝区，第三军医大学西南医院内分泌科） [摘要] 目的 观察雌激素相关受体α (ERRα) 的特异性反向激动剂XCT790对无血清、缺氧及高糖诱导的C57BL/6小鼠骨髓间充质干细胞（MSCs）凋亡的影响，并探讨其作用机制。方法 在3％ O2、无血清、25mmol/L葡萄糖浓度条件下培养MSCs 0～24h，以流式细胞仪检测不同浓度XCT790在缺氧、缺营养、高葡萄糖条件下对MSCs凋亡的影响；Western blot检测bcl-2和bax蛋白表达水平,并计算其比值。结果 缺氧、无血清及高糖干预下，5～20μmol/L XCT790干预组凋亡率显著高于0μmol/L XCT790干预组，呈显著剂量依赖性（P0.05，P0.01）。Western blot显示5～20μmol/L XCT790干预组较0μmol/L XCT790干预组前凋亡蛋白Bax的表达增加，而凋亡蛋白Bcl-2表达降低。Bcl-2/Bax比值在5～20μmol/L剂量范围内随浓度升高而降低，呈显著剂量依赖性（P0.05，P0.01）。结论 缺氧、无血清及高糖诱导下，拮抗ERRα可以使MSCs的凋亡率和Bcl-2/Bax比例明显降低，提示ERRα在细胞耐受凋亡过程中可能发挥重要保护作用。 关键词: XCT790;骨髓间充质干细胞;雌激素相关受体α;凋亡 The Influence of XCT790 on MSCs Apoptosis Induced by Free Serum,Hypoxia and High Glucose Yang Guangxin，Lu Debin，Jiang xiaoyan,Zhao jie,Chen bing （Department of Endocrinology, Southwest　Hospital, Third Military Medical University，Chongqing, 400038, China） [Abstract] Objective To investigate the effect and mechanism of the XCT790 on C57BL/6 mouse bone mesenchymal stem cells（MSCs）apoptosis induced by hypoxia ,serum deprivation and high glucose concentration. Methods MSCs cultured in the condition of hypoxia ,serum deprivation and high glucose concentration were interfered with 0～20μmol/L different concentrations of XCT790. The apoptosis rate was measured by Annexin V-APC /7-AAD on flow cytometer. The expression of Bcl-2 and Bax proteins correlated with apoptosis were detected by Western Blot assay. And the ratio of Bcl-2/Bax was Calculated. Results After being exposed to 5～20μmol/L XCT790 for 0～24h, the apoptosis rates of MSCs was significantly higher than 0μmol/L XCT790 group,increasing in a dose dependent manner（P0.05，P0.01）. The expression of pro-apoptotic protein Bax was increased, while anti-apoptotic protein Bcl-2 was decreased comparing to the control group.And the ratio of Bcl-2/Bax decreased as the dose of XCT790 increased (P0.05，P0.01). Conclusion In the condition of hypoxia ,serum deprivation and high glucose,antagonism of ERRα m