Effects Of Losartan And Simvastatin On The Expressions Of NF-κB,PDGF-B And PKCα In Renal Tissue Of STZ-induced Diabetic Rats

Object The excessive expressions of TGF- , VEGF in renal tissue of diabetic rats has been reported recent years, and the changes can be inhibited with Losartan and Fluvastatin. But exact action mechanism is not very clear. To research the effects of NF- B, PKCa and PDGF-B on the progression of diabetic nephropathy and the renoprotective mechanism of Losartan and Simvastatin on Streptozotocin-induced diabetic Wistar rats, the study item is designed.Methods The 60 Wistar rats were randomly divided into fol lowing 5 groups: normal control (n=8, C group), diabetes control (n=13, D group), diabetic rats treated with Losartan (20 mg kg-1 d-1 , by gavage, n=13, D1 group), diabetic rats treated with Simvastatin(2 mg kg-1 d-1, by gavage, n=13, D2 group) and diabetic rats treated with Losartan and Simvastatin (20 mg kg-1 d-1 and 2 mg kg-1 d-1 , by gavage, n=13, D3 group). All rats of diabetic groups were not treated with insulin or other anti-diabetes drugs. At the end of the 8th week of study, protein expressions of NF- B, PKC a and PDGF-B in kidney were measured by immunohistochemistry, and 12-hour urine albuminuria excretion rate(UAER) , plasma cholesterol plasma triglyceride and plasma creatinine were determined with biochemistry .Results After 8 weeks , the expressions of NF- B, PKC and PDGF-B in diabetic renal tissue were significantly increased(P<0. 05).The means of UAER in diabetic control group was also significant different from other groups and was more than 90 ug/min . The immunohistochemistry staining of NF-KEk PKCaand PDGF-B in kidney proximal tuble cytoplasma is more than that in glomeruler. Epithelial cells of kidney tuble were found vacuolar degeneration with hematoxylin-eosin staining(HE staining) by light microscopy . Both Losartan and Simvastatin can significantly inhibite the expressions of NF-K B, PKCaand PDGF-B in diabetic renal tissue (P<0. 05), but can not make it recovery. Combined treatment of Losartan and Simvastatin can inhibit the expressions of NF-KB, PKCa and PDGF-B further. In general, effects between Losartan and Simvastatin are not significant difference.Conclusion NF-KB, PKCa and PDGF-B play an important action on the progression of diabetic nephropathy. It shouldn' t be ignored that they may injure kidney tuble . Both Losartan and Simvastatin have significant effect on diabetic nephropathy. The renoprotective effect of Losartan is independent upon it' s effect of regulating lipoid metabolism. Combined treatment of Losartan and Simvastatin can further protect kidney from diabetic injury. But their exact mechanism remains to be further studied .