摘要
目的:探讨来氟米特对5/6肾切除大鼠转化生长因子-β1(TGF-β1)表达的影响。方法:将36只SD大鼠随机分为假手术组(A组)12只和手术组24只,术后3d再将手术组大鼠随机分为模型组(B组)12只和来氟米特组(C组)12只。第4,9周末各组随机选取6只大鼠处死并收集标本,记录血肌酐、尿素氮、胆固醇、三酰甘油、白蛋白及24h尿蛋白排泄量;取肾组织做病理检查,用RT-PCR方法测定肾皮质TGF-β1mRNA的表达,免疫组化(SP法)检测TGF-β1在肾脏的表达。结果:(1)与A组相比,B组和C组大鼠造模成功后4周末尿素氮、肌酐、血脂等无明显变化(P>0.05);B组24h尿蛋白排泄量明显增加(P<0.01),血白蛋白下降(P<0.01),肾皮质TGF-β1mRNA表达明显增加(P均<0.05)。9周末B组肾皮质TGF-β1mRNA表达量、尿素氮、肌酐、胆固醇明显增加(P<0.05),24h尿蛋白排泄量增加更为明显(P<0.05)。(2)与B组相比,C组24h尿蛋白排泄量明显下降(P均<0.01);于9周末尿素氮、肌酐、胆固醇明显降低(P<0.05);血白蛋白升高(P<0.05),肾小球硬化指数下降(P<0.01),肾皮质TGF-β1mRNA表达量明显下降(P<0.01)。免疫组织化学染色:B组可见系膜区TGF-β1大量沉积,C组也可见TGF-β1沉积,但较B组明显减轻。结论:来氟米特能减少5/6肾切除大鼠尿蛋白排泄量,纠正其脂代谢紊乱,减轻肾脏的硬化程度,其机制可能与下调系膜细胞上TGF-β1mRNA的表达量及功能活性有关,最终延缓慢性肾脏病的进展。
Objective： To investigate the effects of leflunomide on the expression of TGF-β1 in rats with 5/6 nephrectomy. Methods：Rats were randomly divided into surgery group and pseudo-surgery group（group A）. 3 days after operation, those with 5/6 renal ablation were divide into modal group（ group B） and Leflunomide treated group（group C）. 6 rats of each group were randomly chosen to be sacrificed at the end of the 4th and the 9th week. Samples were collected, including serum creatinine, blood urea nitrogen, cholesterol, triglyceride, 24 - hour urinary protein excretion. Renal TGF-β1 mRNA expression was measured with reverse transcriptase - polymerase chain reaction （RT - PCR）. TGF-β1 was measured with immunohistochemical techniques. Results： （ 1 ）Compared with group A, the blood urea nitrogen, serum creatinine and lipid didn＇t change in group B at the end of 4th week after the animal modals of 5/6 nephrectomy were established successfully （P 〉 0.05）, but 24 - hour urinary protein excretion and renal TGF-β1 mRNA expression were increased significantly （P 〈 0.01 ） while serum albumin was decreased significantly （P 〈 0.01 ） in group B. Those changes were more severe at the end of the 9th week. （2） Compared with group B, serum creatinine, bolld urea nitrogen, cholesterol, 24 - hour urinary protein excretion and renal TGF - β1 mRNA expression were decreased （ P 〈 0.05 ） at the end of the 9th week in group C. TGF-β1 could also be observed in mesangial area by immunohistochemical techniques in group B. In group C these changes alleviated. Conclusion： Leflunomide can decrease the 24 - hour urinary protein excretion, correct the lipid metabolism disorder, and lessen the sclerosis of kidney in the 5/6 nephrectomic rats The mechanism might be related with that leflunomide down - regulating the synthesis and activity of TGF-β1 mRNA.
出处
《中国中西医结合肾病杂志》
2009年第5期409-412,I0004,共5页
Chinese Journal of Integrated Traditional and Western Nephrology
