吡格列酮对5/6肾切除大鼠肾小球硬化与炎性因子表达的影响

The effect of pioglitazone on the expression of Inflammatory factor and Glomerular sclerosis with 5/6 nephrectomy

目的探讨吡格列酮对5/6肾切除大鼠肾小球硬化与炎性因子表达的影响。方法以180~200 g雄性SD大鼠行5/6肾切除建立慢性肾衰竭模型,分为假手术组、模型组和吡格列酮治疗组。术后12周处死大鼠,留取血、尿及肾组织标本。检测各组大鼠血清尿素氮、肌酐及24 h尿蛋白定量,并取残余肾组织做病理检查,采用免疫组织化学方法测定PPARγ、ICAM-1和MCP-1的表达与变化情况。结果与假手术组相比,模型组大鼠血清尿素氮、肌酐及24 h尿蛋白定量均显著升高（均P〈0.01）;免疫组化显示模型组MCP-1和ICAM-1的表达明显升高（均P〈0.01）,PPARγ表达明显下降（P〈0.01）;肾小球系膜区显著增生,肾小球阶段性硬化、近曲小管上皮细胞变性肿胀、间质炎症细胞浸润多见;与模型组相比,吡格列酮治疗组上述生化指标均明显降低（均P〈0.05）,免疫组化显示吡咯列酮组MCP-1和ICAM-1的表达降低（P〈0.05）,PPARγ表达上升（P〈0.05）;肾组织病理损害程度减轻。结论吡格列酮对5/6肾切除大鼠的肾脏有保护作用,其机制可能是通过增强PPARγ表达,下调MCP-1和ICAM-1表达,从而减少细胞增殖、胶原合成和基质堆积等实现的。

【Objective】To discuss the effect of pioglitazone on the expression of Inflammatory factor and glomerular sclerosis with 5/6 nephrectomy.【Method】180~200 g SD rats with 5/6 nephrectomy were randomly divided into sham-operation group, model group, and pioglitazone group. At the 12 th week, taking each group rat＇s blood and urine samples to detect the level of the serum urea nitrogen, creatinine and 24 h urinary protein. Then rats were killed with decapitation method, and residual kidney tissuewas used for pathological examination to observe the expression and variation of PPARγ,ICAM-1and MCP-1 in the kidney tissue of the 6 groups by immunohistochemistry.【Results】Compared with sham-operation group, the model group＇s results of 24 h urine protein, blood urea nitrogen and creatinine were all abnormally increased（P〈0.01）; The expression of MCP-1 and ICAM-1 in the renal tissues of the model group was increased detected by the immunohistochemical, while the level of the PPARγ was decreased in the model group（P〈0.01）. The areas of renal tubular epithelialwere accumulated obviously, the blood capillary were extracted, fiber tissues were proliferated, and the inflammatory cells were seen. Compared with model group,the parameters of biochemical and pathology in pioglitazone group were much better（P〈0.05）, the level of the expression of MCP-1 and ICAM-1 were lower, while the level of the PPARγ was much higher in the pioglitazone group（P〈0.05）.【Conclusions】Pioglitazone could protect the kindney of 5/6 nephrectomy. The mechanism may be related to upregulating the expression of PPARγ, decline the expression of MCP-1,ICAM-1, thus reduce the prolif-eration of cells, the synthesis of collagen, the accumulation of matrix.