Effects of Fluvastatin on Activation of Renal Nuclear Factor-kappa B in Experimental Type 2 Diabetic Rat

Objective:To investigate the effects of fluvastatin on activation of renal NF-κB in type 2 diabetic rat.Methods:A rat model of type 2 diabetic nephropathy(DN) was established successfully by combination of dietary-induced insulin resistance and low-dose STZ-induced hyperglycemia after unilateral nephrectomy.Female SD rats were randomly divided into three groups:control rats、type 2 diabetic rats and type 2 diabetic rats treated with fluvastatin(2 mg·kg-1·d-1).After 6 weeks,blood glucose,serum triglyceride,cholesterol,serum creatinine,and urinary protein were measured respectively.EMSA was used to detect NF-κB activation.RT-PCR technique was used to detect MCP-1 gene expression.Results:Fluvastatin at lower doses,which did not influence blood glucose and lipid level,significantly inhibited expression of NF-κB activation,down-regulated expression of MCP-1 mRNA and lowered urine protein excretion after 6 weeks.Conclusion:Fluvastatin can prevent renal damage in progressive diabetic kidney disease,which is independent from cholesterol-lowering effect.The mechanism may be associated partially with down-regulating renal NF-κB activation and MCP-1 mRNA expression in type 2 DN.