Alpha lipoic acid provides protection on renal tissue fibrosis of diabetic rats by inhibiting activation of TLR4 and NLRP3 inflammatory signal

XIAO Ying1,2 YUAN Zhi-ping3 PENG Can1,2 ZHANG Xiao-huan1,2 ZHANG Ying-ying1,2 WANG Yuan-yuan1,2 SHI Ming-jun1,2 ZHANG Fan1,2 SUN Lan1,2 GUO Bing1,2

(1.Dept of Pathophysiology, Guizhou Medical University, Guiyang, China 550025)
(2.Guizhou Provincial Key Lab of Pathogenesis & Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, China 550025)
(3.Dept of Otolaryngology, City Hospital, Guizhou Medical University, Guiyang, China 550025)
【Knowledge Link】fibrosis

【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 Ⅳ 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, 24 h urine protein, total cholesterol and triglyceride all increased in DM group, and the activity of T-AOC was reduced whereas the 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 the 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.

【Keywords】 diabetic nephropathy; Notch2; Toll-like receptor 4; NLRP3; alpha lipoic acid; inflammation;

【DOI】

【Funds】 United Funding Project of the Department of Science and Technology of Guizhou Province [Guizhou Science and Cooperation LH (2016) 7355] Funding Project for the Growth of Young Scientific and Technological Talents of the Education Department of Guizhou Province [Guizhou Education and Cooperation KY (2017) 165] Funding Project of Guiyang Science and Technology Bureau [Construction and Science (20161001) 42]

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This Article

ISSN:1001-1978

CN: 34-1086/R

Vol 35, No. 03, Pages 335-340

March 2019

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Abstract

  • 1 Materials and methods
  • 2 Results
  • 3 Discussion
  • References