XCT790对缺氧、无血清及高糖诱导骨髓间充质干细胞凋亡的影响  

Effect of XCT790 on MSCs apoptosis induced by serum deprivation,hypoxia and high glucose concentration

作　　者：杨光昕[1] 陆德宾[1] 吴绮楠[1] 赵婕[1] 陈兵[1] 

机构地区：[1]第三军医大学第一附属医院内分泌科,重庆400038

出　　处：《重庆医科大学学报》2015年第7期945-950,共6页Journal of Chongqing Medical University

基　　金：国家自然科学基金青年基金资助项目(编号:81200614)

摘　　要：目的:观察雌激素相关受体α(estrogen-related receptorα,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(mesenchymal stem cells,MSCs)凋亡的影响,并探讨其作用机制。方法:MSCs分为正常培养对照组(正常条件下培养)和0、5、10、20μmol/L XCT790干预组(在3%O2、无血清、25 mmol/L葡萄糖浓度条件下培养),以流式细胞仪Annexin V/7-AAD双染法检测各组在缺氧、缺营养、高葡萄糖条件下的凋亡率;Western blot检测B淋巴细胞瘤-2(B cell lymphoma-2,Bcl-2)和Bax蛋白表达水平,并计算其比值。结果:缺氧、无血清及高糖诱导24 h后,5μmol/L XCT790干预组(20.02±0.92)%、10μmol/L XCT790干预组(26.04±1.24)%、20μmol/L XCT790干预组(50.73±3.55)%的凋亡率明显高于0μmol/L XCT790干预组(14.34±0.61)%,呈剂量依赖性(P<0.05)。Western blot显示,前凋亡蛋白Bax的表达5μmol/L XCT790干预组(0.132 3±0.033 8)、10μmol/L XCT790干预组(0.140 8±0.006 8)、20μmol/L XCT790干预组(0.199 4±0.061 7)较0μmol/L XCT790组(0.116 4±0.017 2)明显升高,而凋亡蛋白Bcl-2表达5μmol/L XCT790干预组(0.069 7±0.013 2)、10μmol/L XCT790干预组(0.051 2±0.005 6)、20μmol/L XCT790干预组(0.041 3±0.005 5)较0μmol/L XCT790组(0.092 3±0.021 3)明显降低(P<0.05)。Bcl-2/Bax比值5μmol/L XCT790干预组(0.530 7±0.027 9)、10μmol/L XCT790干预组(0.397 9±0.004 2)、20μmol/L XCT790干预组(0.234 8±0.032 1)较0μmol/L XCT790组(0.851 7±0.084 4)明显降低,呈剂量依赖性(P<0.05)。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。Objective：To investigate the effects of XCT790 on bone mesenchymal stem cells（MSCs） apoptosis induced by hypoxia,serum deprivation and high glucose concentration. Methods：MSCs were divided into 5 groups：control group（cultrued under normal conditions） and 0-20 μmol/L XCT790 treatment groups（cultured under 3% O2,serum deprivation and 25 mmol/L glucose concentration）. The apoptosis rates were measured by Annexin V-APC /7-AAD on flow cytometry. The protein levels of Bcl-2 and Bax corre-lated with apoptosis were detected by Western blot. And the ratios of Bcl-2/Bax were calculated. Results：After being exposed to 5-20 μmol/L XCT790 for 24 h,the apoptosis rates of 5 μmol/L XCT790 treatment group（20.02±0.92）%,10 μmol/L XCT790 treatment group（26.04±1.24）% and 20 μmol/L XCT790 treatment group（50.73±3.55）% were significantly higher than of 0 μmol/L XCT790 treatment group（14.34±0.61）%,increasing in a dose-dependent manner（P0.05）. Western blot showed the expression of pro-apoptotic protein Bax in 5 μmol/L XCT790 treatment group（0.132 3±0.033 8）,10 μmol/L XCT790 treatment group（0.140 8±0.006 8）and 20 μmol/L XCT790 treatment group（0.199 4±0.061 7） was significantly higher than that in 0 μmol/L treatment group（0.116 4±0.017 2）,while the expression of anti-apoptotic protein Bcl-2 in 5 μmol/L XCT790 treatment group（0.069 7±0.013 2）,10 μmol/L XCT790 treatment group（0.051 2±0.005 6）,20 μmol/L treatment group（0.041 3±0.005 5） was significantly lower than that in 0 μmol/L treatment group（0.092 3±0.021 3）. The Bcl-2/Bax ratios of 5 μmol/L XCT790 treatment group（0.530 7±0.027 9）,10 μmol/L XCT790 treatment group（0.397 9 ±0.034 2） and20 μmol/L XCT790 treatment group（0.234 8 ±0.032 1） were significantly lower than that in 0 μmol/L XCT790 treatment group（0.851 7±0.084 4）,decreasing in a dose dependent manner（P0.05）.Conclusion：In the conditions of hypoxia,serum deprivation and high glucose concentration,antagonism o

关 键 词：XCT790 骨髓间充质干细胞 雌激素相关受体α 凋亡 

分 类 号：R587.1[医药卫生—内分泌]