Effects of fluvastatin on the tubulointerstitium in progressive diabetic kidney disease

Objective To investigate the effects of fluvastatin on the tubulointerstitium damage in progressive diabetic kidney disease. Methods A rat model of type 2 diabetic nephropathy (DN) was developed 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 (2mg/kg/d). After 6 weeks, blood glucose, serum insulin, serum triglyceride and cholesterol, serum creatinine, and urinary protein were measured respectively. The protein expressions of c Jun and tansforming growth factor (TGF) β 1 were studied by immunohistochemistry. TGF β 1 gene expression was studied with a RT PCR technique. Results Fluvastatin at lower doses, which did not influence blood glucose and blood lipid level, significantly inhibited expression of c Jun protein(0 2536±0 0180 vs 0 5855±0 0314, P 0 01), down regulated expression of TGF β protein(0 1835±0 0047 vs. 0 3973±0 0052, P 0 01)and its mRNA(0 2553±0 00215 vs. 0 8932±0 0363, P 0 01) and lowered urine protein excretion (0 1835±0 0047 vs. 26 53±7 33, P 0 05) after 6 weeks. Conclusions Fluvastatin can prevent tubulointerstitium damage in progressive diabetic kidney disease independent of cholesterol lowering effects. The mechanism may be associated, at least in part, with down regulating the AP 1(c fos / c Jun)and TGF β 1 expression in tubulointerstitium in type 2 DN.