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

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·d1,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(P0.05 or P0.01) in diabetic rats than in normal control rats.Simvastatin significantly reduced theses parameters(P0.05 or P0.01).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(P0.01),and the expressions were decreased by simvastatin(P0.01).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.