吡格列酮对肥胖小鼠肾脏中TNF-α表达的影响

Effects of pioglitazone on the expression of TNF-α in kidney of obese mice

目的:研究吡格列酮对肥胖小鼠肾脏中肿瘤坏死因子-α(TNF-α)表达的影响,探讨肥胖相关性肾病的防治意义。方法:选用OB小鼠和C57小鼠(作为对照组)进行对比观察,并将OB小鼠分为模型组和治疗组,治疗组给予吡格列酮灌胃,连续10周,实验前后测定小鼠血糖,尿微量白蛋白(mALB)。10周末处死小鼠,摘取双侧肾脏,免疫组化方法测定TNF-α表达水平,比较3组小鼠之间测定指标的差异并进行相关性分析。结果:OB小鼠的mALB、TNF-α阳性百分比均明显高于C57小鼠,差异有统计学意义(P<0.01);给予吡格列酮干预后,治疗组尿mALB、TNF-α阳性百分比均低于模型组,差异有统计学意义(P<0.01)。结论:TNF-α在肥胖小鼠肾小管上皮细胞、肾小球系膜细胞的表达水平较普通小鼠明显升高,吡格列酮可以下调TNF-α在肥胖小鼠肾脏中的表达水平,从而减少尿mALB排泄。

Objective：To study the effects of pioglitazone on the expression of tumor necrosis factor-α（TNF- α） in the kidney of obese mice and to explore the prevention of obesity related glomerulopathy. Methods： The OB mice and C57 mice（as control group） were observed, and OB mice were divided into model group and treatment group, and the latter was given pioglitazone orally for 10 weeks. Before and after the experiment, blood glucose and uninary microalbumin（m ALB） in mice were measured. Mice were sacrificed at week 10, both kidneys were removed, and TNF-α expression level was determined by immunohistochemical method. The indicators were compared among3 groups of mice, and the correlations were calculated. Results： OB mice urinary m ALB and TNF- α positive percentage were significantly higher than those of C57 mice（ P〈0.01）; pioglitazone intervention treatment group, urinary m ALB and TNF- α positive percentages were lower than those in the model group, and the difference was statistically significant（P〈0.01）. Conclusion： The expression level of TNF-α in obese mice renal tubular epithelial cells, mesangial cells significantly are increased than normal mice and pioglitazone can lower the expression level of TNF-α in kidney of obese mice, thus reducing urinary albumin excretion.