罗格列酮对高糖刺激下肾小管上皮细胞凋亡及整合素β_1表达的影响

Effect of Rosiglitazone on Integrin β_1 Expression and Apoptosis of Proximal Tubular Cell Exposed to High Glucose

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(5mmol/L)组、高糖(30mmol/L)组、ROS(10μmol/L)组、高糖(30mmol/L)+ROS(5μmol/L)组和高糖30mmol/L+ROS10μmol/L6组,采用流式细胞仪检测细胞培养后24、48、72h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integrinβ1的表达较高糖组降低,且与ROS浓度呈剂量相关。各实验组在48h、72h的细胞凋亡率与空白对照组相比均降低(P<0.05);48、72h的细胞凋亡率低于24h(P<0.05),但48h与72h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。

Objective To evaluate the effect of rosiglitazone （ROS） on integrin 6x 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 μmol/L） group, glucose （30 mmol/L）＋ROS （5 μmol/L） group, and glucose （30 mmol/L） ＋ ROS （10 μmol/L） group. The cells were cultured for 48 hrs and the integrin β1 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 β1 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 β1 of glucose （30 mmol/L）＋ROS （5 or 10 μmol/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 β1 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 β1.