VD3调控ROS介导的TXNIP/NLRP3通路抑制高糖诱导肾系膜细胞纤维化的机制研究

doi:10.3969/j.issn.1006-6233.2024.05.011

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Abstract Objective: To investigate the effect of active vitamin D3 (VD3) on the characteristics of renal mesangial cell fibrosis induced by high glucose, and to explore the relevant mechanism. Methods: Rat mesangial cell line HBZY-1 was cultured and divided into normal glucose culture (NG) group, normal glucose combined with VD3 culture (NG+VD3) group, high glucose culture (HG) group, high glucose combined with VD3 culture (HG+VD3) group, high glucose combined with n-acetylcysteine culture (HG+NAC) group. The proliferation activity of cells in each group was detected by CCK-8 method, the apoptosis rate of cells in each group was detected by flow cytometry, the content of reactive oxygen species (ROS) in cells in each group was detected by DCFH-DA method, the levels of interleukin-1β (IL-1β), IL-18 and tumor necrosis factor-α (TNF-α) in cell supernatant were detected by enzyme-linked immunosorbent assay (ELISA), the mRNA expression and the protein expression of transforming growth factor-β1 (TGF-β1), fibronectin (FN), intercellular adhesion molecule-1 (ICAM-1), thioredoxin interacting protein (TXNIP), NOD-like receptor heat protein domain associated protein 3 (NLRP3) in cells in each group were detected by real-time fluorescent quantitative polymerase reaction (RT-qPCR) and Western blot. Results: Compared with NG group, the proliferative activity in HG group was significantly increased (P<0.05), the apoptosis rate was significantly decreased (P<0.05), ROS content was significantly increased (P<0.05), the levels of IL-1β, IL-18 and TNF-α in cell supernatant were significantly increased (P<0.05), and the mRNA and protein relative expression levels of TGF-β1, FN, ICAM-1, TXNIP and NLRP3 were significantly up-regulated (P<0.05). Compared with HG group, the proliferative activity in HG+VD3 and HG+NAC groups was significantly decreased (P<0.05), the apoptosis rate was significantly increased (P<0.05), the ROS content was significantly decreased (P<0.05), the levels of IL-1β, IL-18 and TNF-α in cell supernatant were significantly decreased (P<0.05), and the mRNA and protein relative expression levels of TGF-β1, FN, ICAM-1, TXNIP and NLRP3 were significantly down-regulated (P<0.05). Conclusion: VD3 can alleviate hyperglycemia-induced hyperproliferation and fibrosis of renal mesangial cells, which may be related to the regulation of ROS/TXNIP/NLRP3 pathway.

Key words： Diabetic nephropathy Mesangial cells of kidney Active vitamin D3 Proliferation Fiber

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2024.05.011 OR http://www.hbyxzzs.cn/EN/Y2024/V30/I5/762

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