辛伐他汀对Ⅰ型糖尿病大鼠的肾脏保护作用及对肾脏组织Toll样受体4和MCP-1表达的影响

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。

The protective effect of simvastatin on kidney and its impact on expressions of TLR4 and MCP-1 in kidney tissues of type 1 diabetic rats

Objective To explore the protective effect of simvastatin on kidney and its impact on expressions of TLR4 and MCP-1 in kidney tissues of type 1 diabetic rats.Methods Fifty-four Wistar rats were divided into three groups: normal control,diabetes and simvastatin treated groups.The blood glucose,serum insulin and 24h urinary protein were respectively determined in these groups at 4,8 and 12 weeks.In addition,the mRNA expressions and proteins of TLR4 and MCP-1 in the kidney tissues were respectively detected by using real time PCR(RT-PCR) and immunohistochemistry.The changes in ultrastructure of kidney tissues were observed under electron microscope in week 4,8,12.Results ①Compared with the normal control group,the diabetic group had a significant increase in the blood glucose,24h urinary protein excretion(P<0.05),the mRNA expressions and proteins of TLR4 and MCP-1 in kidney tissues(P<0.05),but serum insulin had a decrease(P<0.05).The glomerular basement membrane was remarkably thickened.The mesangium and mesangial cells showed significant proliferation under electron microscope.②The simvastatin treated group had a obviously decrease in all the data mentioned above(P<0.05);but the values tended to be higher as compared with the normal control group(P<0.05).The pathological findings were also significantly improved,although something different from normal level.Conclusion Simvastatin may protect against kidney injury in diabetes through downregulating the expressions of TLR4 and MCP-1,hence inhibition of inflammatory reaction and reduing the kidney damage.