罗格列酮对高糖刺激下肾小管上皮细胞凋亡及整合素β1表达的影响

目的 观察罗格列酮(ROS)对肾小管上皮细胞凋亡及整合素β1 (integrin β1)水平的影响.方法 将体外培养的大鼠近端肾小管上皮细胞分为空白对照组、正常血糖(5 mmol/L)组、高糖(30 mmol/L)组、ROS (10 μmol/L)组、高糖(30 mmol/L) ROS (5 μmol/L)组和高糖30 mmol/L ROS 10 μmol/L 6组, 采用流式细胞仪检测细胞培养后24、48、72 h的凋亡情况、Western blot及RT-PCR检测不同浓度的ROS对高糖刺激下integrin β1蛋白质和mRNA表达的影响.结果 integrin β1的蛋白质和mRNA的改变趋势相同,高糖组较对照组及正常血糖组增加(P＜0.05) ,经ROS处理后integrin β1的表达较高糖组降低,且与ROS浓度呈剂量相关.各实验组在48 h、72 h的细胞凋亡率与空白对照组相比均降低(P＜0.05);48、72 h的细胞凋亡率低于24 h(P＜0.05),但48 h与72 h间的比较差异无统计学意义.结论 ROS可明显抑制高糖刺激下肾小管上皮细胞integrin β1的表达,且有明显剂量依赖关系,而ROS对细胞凋亡的影响可能与 integrin β1的参与有关.

Effect of Rosiglitazone on Integrin β1 Expression and Apoptosis of Proximal Tubular Cell Exposed to High Glucose

OBJECTIVE: To evaluate the effect of rosiglitazone (ROS) on integrin beta1 expression and apoptosis of proximal tubular cell exposed to high glucose. METHODS: The proximal tubular cells of rats were cultured in vitro and divided into 6 groups: control group, normal glucose (5 mmol/L) group, high glucose (30 mmol/L) group, only ROS (10 micromol/L) group, glucose (30 mmol/L)+ROS (5 micromol/L) group, and glucose (30 mmol/L) +ROS (10 micromol/L) group. The cells were cultured for 48 hrs and the integrin beta1 expressions were detected by Western blot and RT-PCR; The apoptosis was evaluated by flow cytometry after the cells were cultured for 24, 48, 72 hrs. RESULTS: The expressions of integrin beta1 protein and mRNA of high glucose (30 mmol/L) group were significantly increased as compared with control group and normal glucose (5 mmol/L) group. The integrin beta1 of glucose (30 mmol/L)+ROS (5 or 10 micromol/L) group was decreased as compared with high glucose group (P < 0.05). Flow cytometry demonstrated the decreased apoptosis to be with time-dependence. CONCLUSION: ROS can strikingly inhibit the expression of integrin beta1 in proximal tubular cells exposed to high glucose, with a marked dose-dependent manner. The effect of ROS on cell apoptosis may be relevant to integrin beta1.