[Alpha-lipoamide inhibits renal inflammation and collagen 4 production in diabetic rats and its mechanism].

Objective To observe the expression of Notch2, NLR family pyrin domain containing 3 (NLRP3) in the renal tissue of rats with diabetes mellitus (DM), and the effects of alpha-lipoamide (ALM) on the expression of Notch2, Toll-like receptor 4 (TLR4), NLRP3 and collagen, to explore the possible protective mechanism of ALM against diabetic renal inflammation and renal fibrosis. Methods The DM rat models were induced by the injection of streptozotocin (STZ) and divided into DM group and ALM group. Meanwhile, normal control (NC) group was set up. There were 8 rats in each group. Two weeks after the successful establishment of DM model, ALM [150 mg/(kg.d)] was given intragastrically to the rats in the ALM group, and the rats were sacrificed 6 weeks later. The morphologic changes of renal tissues were observed by HE and Masson staining. The expression and localization of Notch2, TLR4 and NLRP3 in the renal tissues were detected by immunohistochemical staining. The protein levels of Notch2, TLR4, NLRP3 and collagen 4 (Col4) were determined by Western blot analysis. The levels of interleukin 6 (IL-6) and tumor necrosis factor (TNF-α) in the renal tissue homogenates were measured by ELISA. Spearman rank correlation test was used to analyze the correlation between Notch2, TLR4 and NLRP3 protein expression. Results Compared with the NC group, the levels of blood glucose, 24-hour urine protein, kidney index, total cholesterol and triglyceride in the DM group significantly increased, while compared with the DM group, those in the ALM group were significantly reduced, but there was no significant change in blood glucose. Compared with the NC group, the protein levels of Notch2, TLR4, NLRP3 and Col4 in the renal tissues of the DM group increased. As same as the levels of Notch2, TLR4, NLRP3 and Col4 in the ALM group, the levels of IL-6 and TNF-α in the renal homogenates of the ALM group were significantly lower than those of the DM group. Correlation analysis showed that there was a significant positive correlation between the expressions of Notch2 and TLR4 in the DM group and ALM group, and the expression of Notch2 and NLRP3 were also significantly positively correlated. Conclusion ALM alleviates the renal inflammation and Col4 production in diabetic rats, which is related to the Notch2-induced inhibition of TLR4 and NLRP3 activation.