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目的研究辛伐他汀对1型糖尿病大鼠的肾脏保护作用及对肾脏组织Toll样受体(TLR)4和单核细胞趋化蛋白-1(MCP-1)表达的影响。方法将54只Wistar大鼠随机分为正常对照组、糖尿病组和辛伐他汀干预组。在实验的第4、8、12周分别检测每组大鼠的血糖、血清胰岛素、24h尿白蛋白量,免疫组织化学法和实时荧光定量聚合酶链反应法(RT-PCR)分别检测肾脏组织TLR4和MCP-1蛋白及mRNA的表达。在电镜下观察第4、8、12周大鼠肾脏组织超微结构的改变。结果①与正常对照组相比,糖尿病组的血糖、24h尿白蛋白量均明显升高(P<0.05),血清胰岛素明显降低(P<0.05),肾脏组织中TLR4和MCP-1蛋白及mRNA的表达也显著增加(P<0.05)。电镜下糖尿病组的肾小球系膜和系膜细胞均显著增生,基底膜明显增厚。②辛伐他汀干预组的上述指标均较糖尿病组有明显降低(P<0.05),但与正常对照组相比仍有增高(P<0.05)。肾脏组织的病理改变亦有所减轻,但与正常对照组相比仍有改变。结论辛伐他汀对1型糖尿病大鼠肾脏具有一定的保护作用,其可能的机制是通过减少TLR4和MCP-1的表达,从而抑制炎症反应,减少肾脏损伤。
Objective To investigate the protective effects of simvastatin on type 1 diabetic nephropathy and its effect on the expression of toll like receptor (TLR) 4 and monocyte chemoattractant protein-1 (MCP-1) in kidney. Methods 54 Wistar rats were randomly divided into normal control group, diabetic group and simvastatin intervention group. At the 4th, 8th and 12th week of the experiment, the blood glucose, serum insulin, 24h urinary albumin were detected in each group, and the renal tissues were detected by immunohistochemistry and real-time fluorescence quantitative polymerase chain reaction (RT- TLR4 and MCP-1 protein and mRNA expression. The changes of ultrastructure of kidney in the 4th, 8th and 12th weeks were observed under the electron microscope. Results ① Compared with the normal control group, the levels of blood glucose and 24h urinary albumin in diabetic group were significantly increased (P <0.05) and the levels of serum insulin were significantly decreased (P <0.05). The expressions of TLR4 and MCP-1 protein and mRNA The expression was also significantly increased (P <0.05). Under electron microscope, glomerular mesangial cells and mesangial cells in diabetic group were significantly hyperplasia, basement membrane was significantly thicker. ② Simvastatin intervention group above indicators were significantly lower than the diabetic group (P <0.05), but still higher than the normal control group (P <0.05). Pathological changes in kidney tissue also eased, but still change compared with the normal control group. Conclusion Simvastatin has a protective effect on the kidney of type 1 diabetic rats. Its possible mechanism is that it inhibits the inflammatory reaction and reduces the renal damage by decreasing the expression of TLR4 and MCP-1.