Abstract: Abstract：Objective To observe the changes of A20 in mesangial cells of diabetic nephropathy (DN) rat model in⁃ duced by lipopolysaccharide (LPS)- rat, and to explore its possible mechanism. Methods (1)Thirty health male Wistar rats were randomly divided into two group. Model rats were given streptozotocin (STZ) at a dose of 60 mg/kg by intraperitoneal in⁃ jection. Rats in the control group received the same volume of citrate buffer in the same way. Levels of blood glucose and uri⁃ nary microalbumin were detected in two groups at the 6th and the 8th week. Changes of renal pathology were observed by HE staining. Changes of protein A20 were observed by immunohistochemistry. (2) Expression changes of gene and proteins A20, nuclear factor (NF)-κB, IκB, IKKγ and MCP-1 in renal cells treated with LPS were determined after treatment with different time points (0, 2, 4, 6, 12, 24, 48 and 72 h) and different concentrations (0.1, 1 and 10 μg/L). Results (1) Levels of blood glucose and urinary microalbumin were significantly increased in model group compared with those of control group (P < 0.01). HE stainig showed that hyaline degeneration in tubular epithelial cells was found in model group, especially at the 8th week. Results of immunohistochemistry showed that expression of protein A20 significantly decreased in kidney tubules and nearly disappeared in glomerulus in model group compared with that of control group, which expressed less at the 8th week. (2) There was no significant difference in the expression of IKKγ between different concentrations and different times. Com⁃ pared with 0 h, the expression of A20 protein was increased at 2 h and 4 h, except that the expression of A20 protein in⁃ creased after 6 h (P < 0.05). Meanwhile NF-κB expression increased and IκB expression decreased in different time points (P < 0.05). In addition, the expressions of A20 and IκB were decreased concentration-dependently (P < 0.05). The expres⁃ sion levels of NF-κB and MCP-1 were increased concentration-dependently (P < 0.05). Conclusion A20 may involve in the development of diabetic nephropathy by regulating the NF-κB pathway.

Key words: diabetic nephropathy, mesangial cells, lipopolysaccharides, blood glucose, NF-kappa B, micro albuminuria, A20 gene