Alpha lipoic acid provides protection on renal tissue fibrosis of diabetic rats by inhibiting activation of TLR4 and NLRP3 inflammatory signal / 中国药理学通报

ABSTRACT

Aim: To investigate the effects of alpha lipoic acid (ALA) on Notch2, TLR4, NLRP3 and inflammatory factor expression in renal tissues of diabetes mellitus(DM) rats, and to explore its possible mechanism of anti-inflammatory and anti-fibrosis by Alpha lipoic acid. Methods: The diabetic rat model was established by streptozotocin. The rats were divided into two groups; the DM group and ALA group. Meanwhile, and another eight rats were used as normal control (NC group). After eight weeks, the rats were sacrificed to detect the relevant biochemical parameters and oxidative stress indexes. In addition, immunohistochemical staining was employed to detect the protein expression localization sites of Notch2, TLR4 and NLRP3. Western blot analysis was used to detect the expression of Notch2, TLR4, NLRP3 and collagen FV proteins in renal tissues. ELISA was utilized to detect the inflammatory factor expression of IL-6 and TNF-α. Results: Compared with NC group, the levels of blood glucose, 24h urine protein, total cholesterol and triglyceride all increased in DM group, and the activity of T-AOC was reduced whereas MDA content was up-regulated in DM group, all items but blood glucose were significantly reduced in ALA group, and the activity of T-AOC remarkably increased, while MDA content was reduced in ALA group. Compared with NC group, the protein levels of Notch2, TLR4, NLRP3 and collagen IV in kidneys were raised, and the inflammatory factor expression of IL-6 and TNF-α significantly increased in DM group. Conclusions: ALA may down-regulate the inflammatory signal of TLR4 and NLRP3 in kidney of diabetic rats, and reduce the expression of inflammatory factor and the accumulation of extracellular matrix via inhibiting the expression of Notch2 at protein level.