空军军医大学学报2024,Vol.45Issue(8):913-919,7.DOI:10.13276/j.issn.2097-1656.2024.08.014
二十碳五烯酸对糖尿病肾足细胞损伤保护机制研究
Protective mechanism of eicosapentaenoic acid on diabetic kidney podocyte injury
摘要
Abstract
Objective To investigate the role and potential mechanism of eicosapentaenoic acid(EPA)in simulating high glucose-induced kidney podocyte injury.Methods Mouse MPC5 kidney podocytes were cultured in vitro and induced by high glucose,and then treated with different concentrations of EPA.The viability of MPC5 cells was assessed by CCK-8 assay,apoptosis was analyzed by flow cytometry,expressions of apoptotic proteins and podocyte marker proteins were detected by Western blotting,reactive oxygen species(ROS)production after high glucose stimulation was analyzed by ROS fluorescent probe assay,and secretion of inflammatory factors was further detected by ELISA.Results CCK-8 cell viability showed that EPA maintained high glucose-induced cell viability,and the expression of podocyte marker proteins podocin and synaptopodin was significantly higher after EPA intervention(P<0.05,P<0.01).Flow cytometry analysis showed that apoptosis of high glucose-stimulated podocytes was significantly decreased after EPA intervention(P<0.01),the expressions of pro-apoptotic proteins Bax and cleaved Caspase-3 were decreased(P<0.05,P<0.01),and the expression of anti-apoptotic protein Bcl-2 was increased(P<0.01).ROS production was significantly decreased after EPA intervention compared with the high glucose group(P<0.01),and ELISA results showed that EPA intervention decreased high glucose-induced secretion of TNF-α,IL-1 β and IL-6 inflammatory factors(P<0.01).After EPA intervention,the inflammatory signaling pathway proteins TLR4 and MYD88 protein were reduced(P<0.05,P<0.01),and the expression of lipid metabolism protein SREBP1 was decreased after EPA intervention(P<0.05,P<0.01).After overexpression of SREBP1,the above assay results of EPA on high glucose-induced MPC5 cells were reversed.Conclusion EPA can inhibit ROS production in podocytes stimulated by high glucose and reduce podocyte apoptosis,while EPA may inhibit the activation of inflammatory pathways by regulating SREBP 1,thereby playing a protective role in diabetic kidney podocytes.关键词
糖尿病肾病/二十碳五烯酸/足细胞损伤/SREBP1Key words
diabetic nephropathy/eicosapentaenoic acid/podocyte injury/SREBP1分类
医药卫生引用本文复制引用
张磊,于芳,曹瑞,王晓慧,徐孝娜,王枫,刘寒强..二十碳五烯酸对糖尿病肾足细胞损伤保护机制研究[J].空军军医大学学报,2024,45(8):913-919,7.基金项目
陕西省自然科学基金面上项目(2021JM-240) (2021JM-240)