Abstract: Objective To investigate the correlation between NF-κB/COX-2 signal pathway and cell proliferation in diabetic nephropathy. Methods Uninephrectomized STZ-induced male Wister rats were used. Using immunohistochemistry to detect NF-κB and COX-2 protein expressions in diabetic kidneys at the week of 16 . HKC were cultured separately in normal or high glucose medium for 24,48,72h.The expression of NF-κB and COX-2 protein was detected by flow cytometry and the expression of PCNA was detected by immunocytochemical staining. Results 1 Volum of glomeruli, mesangial matrix, thickness of glomerular and tubular basement membrane increased in diabete group; 2 COX-2 were positively expressed in cytoplasm of tubules and glomeruli by immunohistochemistry. Compared with control group, the expression of COX-2 was higher; activated NF-κB were positively expressed in nucli of both tubules and glomeruli, There was weak stainings for in control group, while enhanced stainings were observed in DM, there was positive correlation between NF-κB and COX-2. 3 Compared with those in HKC cultured in the medium with normal level glucose, the stainings were strengthened for PCNA in HKC exposed to high glucose from 24h . 4 By FCM , the expression of NF-κB and COX-2 in HKC cultured in high glucose medium was higher than that in normal glucose medium ; the expression of NF-κB and PCNA was positively correlated with the expression of COX-2. Conclusion Activating NF-κB and elevating the expression of COX-2 play an important role in regulating cell proliferation , which may be one of the injury mechanisms of the renal cells during diabetic nephropathy.

Key words: diabetic nephropathy, proliferation, nuclear factor-kappa B, cyclooxygenase 2