中文摘要：

目的 探讨瑞舒伐他汀对肿瘤坏死因子-α（TNF-α）诱导的人骨髓间充质干细胞（MSC）凋亡的影响及其机制.方法 以TNF-α诱导建立MSC凋亡的模型,分为对照组（以PBS干预）、TNF-α组（TNF-α干预6h）、TNF-α＋他汀组（瑞舒伐他汀预处理后,TNF-α干预）、TNF-α＋他汀＋antago-miRNA组（先予antago-miRNA-210转染MSC,之后干预同TNF-α＋他汀组）.采用MTT法、TUNEL以及caspase-3活性检测法比较各组MSC凋亡水平.以实时定量聚合酶链反应检测MSC内miRNA-210的表达水平.结果 TNF-α＋他汀组MSC内caspase-3活性低于TNF-α组（1.63±0.25比2.05±0.36,P＜0.05）,TUNEL法提示TNF-α＋他汀组凋亡水平低于TNF-α组[（16.87±9.27）％比（33.74±6.57）％,P＜0.05].TNF-α干预呈浓度依赖性地降低MSC胞内miRNA-210表达水平.而TNF-α＋他汀组MSC内miRNA-210表达水平高于TNF-α组（P＜0.05）.TUNEL法提示TNF-α＋他]＋ antago-miRNA组细胞凋亡率高于TNF-α＋他汀组[（42.58±6.71）％比（16.87±9.27）％,P＜0.05],同时TNF-α＋他汀＋antago-miRNA组胞内caspase-3水平高于TNF-α＋他汀组（2.31 ±0.22比1.77±0.33,P＜0.05）.结论 瑞舒伐他汀预处理可改善TNF-α诱导的MSC凋亡情况,而miRNA-210参与介导了这一抗凋亡的保护作用.

英文摘要：

Objective To explore the effect and mechanism of rosuvastatin on tumor necrosis factor-α induced human mesenchymal stem cells （MSCs） apoptosis.Method Human MSCs were treated as follows：（1） culture medium; （2） TNF-α （20 μg/ml） for 6 h; （3） rosuvastatin （20 μmol/L） for 24 h; （4）rosuvastatin （20 μmol/L） for 24 h followed by TNF-α （20 μg/ml） for 6 h ; （5） TNF-α ＋ rosuvastatin ＋ 50nmol/L antago-miRNA; （6） TNF-α ＋ rosuvastatin ＋ 100 nmol/L antago-miRNA.Cell survival and apoptosis were determined by MTT,TUNEL and caspase-3 activity assay.The changes of miRNA-210 in each group were detected with quantitative PCR.Result TNF-α significantly induced human MSCs apoptosis in a concentration-dependent manner,and pretreatment with rosuvastatin significantly reduced MSCs apoptosis （caspase-3 assay：TNF-α ＋ Statin group vs.TNF-α group：（1.63 ± 0.25） vs.（2.05 ± 0.36）,P ＜ 0.05）.Meanwhile,TNF-α progressively reduced the expression of miRNA-210 in human MSCs in a dose-dependent manner,while the miRNA-210 expression was significantly upregulated in TNF-α ＋ Statin group （P ＜ 0.05）.The protective effect of rosuvastatin on TNF-α induced MSCs apoptosis was largely abolished by co-treatment with 100 nmol/L antago-miRNA（TUNEL：TNF-α ＋ Statin ＋ antago-miR group vs.TNF-α ＋Statin group：（42.58 ±6.71）％ vs.（16.87 ±9.27）％,P ＜ 0.05）.Conclusion Pretreatment with rosuvastatin can significantly improve the viability of human MSCs after TNF-α injury,the protective mechanism of rosuvastatin is partly mediated through miRNA-210 up-regulation.