辛伐他汀对糖尿病大鼠的肾脏保护作用及其抗炎机制探讨

Reno-protective effect of simvastatin through an anti-inflammatory mechanism in streptozotocin-induced diabetic rats

目的:研究辛伐他汀对糖尿病大鼠的肾脏保护作用及其相关的抗炎机制。方法:将Wistar大鼠随机分为正常对照、糖尿病模型组和辛伐他汀治疗组,每组8只。腹腔注射链脲佐菌素65 mg.kg-1建立糖尿病大鼠模型1周后,灌胃辛伐他汀20 mg.kg-1.d-1,qd,连续灌胃7周。正常对照组和糖尿病模型组灌以等体积的生理氯化钠溶液。第8周时,监测各组鼠尾外周血血糖,检测大鼠血糖化血红蛋白(HbA1c)及12 h尿白蛋白(UALB)、视黄醇结合蛋白(URBP)和尿单核细胞趋化蛋白-1(UMCP-1)、尿细胞间黏附分子-1(UICAM-1)的排泄率,处死大鼠留取肾脏标本,计算肾脏肥大指数、电镜下病理学检查,并采用逆转录PCR(RT-PCR)法和实时定量PCR(real-time PCR)法对肾脏组织表达的MCP-1和ICAM-1mRNA进行半定量和相对定量检测。结果:第8周时,与正常对照组比较,糖尿病模型大鼠的血糖、HbA1c、UALB、URBP、UMCP-1、UICAM-1排泄率和肾脏肥大指数水平均显著升高(P<0.05或P<0.01),电镜下肾组织结构病变明显,肾组织MCP-1和ICAM-1 mRNA表达均明显上调(P<0.01);与糖尿病模型组比较,辛伐他汀治疗组除血糖和HbA1c水平外,其他各项生化指标和肾脏肥大指数均明显降低(P<0.05或P<0.01),肾组织病理改变明显减轻,肾组织MCP-1和ICAM-1 mRNA表达均显著下降(P<0.01)。结论:辛伐他汀对糖尿病大鼠肾脏具有确切的保护作用,其机制可能通过降低MCP-1和ICAM-1的表达和排泄,减轻微炎症反应有关。

Objective： To investigate the reno-protective effect of simvastatin in streptozotocin（STZ）-induced diabetic rats,and the association with inflammatory reaction.Methods： In 24 Wistar rats,diabetes mellitus was induced by STZ（65 mg·kg^-1）.One week after the diabetes mellitus was established,oral simvastatin（20 mg·kg^-1·d^-1,qd,for 7 weeks） was administered,and saline was used as the control.Blood glucose and HbA1c,were measured,and the urinary excretions of albumin（ALB）,retinal binding-protein（RBP）,monocyte chemoattractant protein-1（MCP-1） and intercellular adhesion molecule-1（ICAM-1） were tested 8 weeks after the treatment.The renal tissues of diabetic rats were obtained for evaluating the pathological changes,such as the relative kidney index,the alterations under an electron microscope,and the mRNA expressions of MCP-1 and ICAM-1.Results： At 8 weeks after the treatment,the blood glucose and HbA1c levels,and urinary excretions of ALB,RBP,MCP-1,ICAM-1,as well as the relative kidney index were significantly higher（P〈0.05 or P〈0.01） in diabetic rats than in normal control rats.Simvastatin significantly reduced theses parameters（P〈0.05 or P〈0.01）.Simvastatin also attenuated the pathological lesions in the kidney as observed by electron microscopy,but did not completely reverse the lesion.The mRNA expressions of MCP-1 and ICAM-1 were significantly up-regulated in the kidney of diabetic rats as compared with normal control（P〈0.01）,and the expressions were decreased by simvastatin（P〈0.01）.Conclusions： Simvastatin has a protective effect on the renal tissue injury in STZ-induced diabetic rats,which may partly relate to its anti-inflammatory activity via reducing the expression and excretion of MCP-1 and ICAM-1.