PGC-1α对线粒体氧化应激反应及人肾皮质近曲小管上皮细胞焦亡的影响  

Effects of PGC-1α on mitochondrial oxidative stress and pyroptosisin human renal cortical proximal tubular epithelial cells

作　　者：丁艳玲 王妍君 罗朋立 DING Yanling;WANG Yanjun;LUO Pengli(Qinghai University,Xining 810016,China;Department of Nephrology,Affiliated Hospital of Qinghai University,Qinghai Provincial Clinical Research Center for Chronic Kidney Disease,Xining 810001,China)

机构地区：[1]青海大学,西宁810016 [2]青海大学附属医院肾病内科,青海省慢性肾脏病临床医学研究中心,西宁810001

出　　处：《中国高原医学与生物学杂志》2024年第4期271-281,共11页Journal of Chinese High Altitude Medicine & Biology

基　　金：青海省科技厅应用基础研究项目(批准号:2022-ZJ-759)。

摘　　要：目的探讨PGC-1α对线粒体氧化应激反应及人肾皮质近曲小管上皮(HK-2)细胞焦亡的影响。方法将HK-2分为对照组(Con组。21%氧气)和缺氧/复氧组(Hyp-R组。用1%氧气培养12 h后立刻用21%氧气培养12 h)、缺氧/复氧组加溶剂对照组(Hyp-R+S组。用1%氧气培养12 h,加入DMSO溶液后立刻用21%氧气培养12 h)、缺氧/复氧组加药物干预组(Hyp-R+ZLN组。用1%氧气培养12 h,加入PGC-1α激动剂ZLN005后立刻用21%氧气培养12 h)。检测各组细胞凋亡率、活性氧含量、线粒体膜电位水平和细胞上清液中IL-10、IL-18的含量,以及细胞焦亡相关蛋白表达水平和线粒体动力学相关蛋白表达水平。观察各组细胞及线粒体形态结构。结果1.Hyp-R组与Con组相比,Caspase-1、Nlrp3、GSDMD-N、Drp1蛋白表达增多(P<0.05),细胞上清液中IL-18的分泌增多(P<0.05),细胞晚期凋亡率升高(P<0.05),活性氧含量增多(P<0.05),JC-1单聚体荧光含量增多(P<0.05)。2.Hyp-R+ZLN组与Hyp-R组相比,细胞焦亡相关蛋白表达减少,细胞上清液中IL-18的分泌减少(P<0.05),活性氧含量减少(P<0.05),JC-1单聚体荧光含量减少(P<0.05)。3.Hyp-R组的线粒体肿胀、线粒体嵴溶解,细胞具有部分疑似焦亡的特征;Hyp-R+ZLN组被破坏的细胞及线粒体结构得以修复。结论PGC-1α通过调控线粒体生物合成改善线粒体功能、影响HK-2细胞焦亡。ObjectiveeTo investigate the effects of PCC-lαon mitochondrial oxidative stress and human renal tubular epithelial(HK-2)cell pyroptosis.Methods HK-2 cells were divided into control group(Con group.21%oxygen),hypoxia/reoxygenation group(Hyp-R group,incubated with 1%oxygen for 12 h and immediately incubated with 21%oxygen for 12 h),hypoxia/reoxygenation plus solvent control group(Hyp-R+S group,incubate with 1%oxygen for 12 h and immediately after addition of DMSO solution,incubate with 21%oxygen for 12 h)and hypoxia/reoxygenation plus drug intervention group(Hyp-R+ZLN group,incubated with 1%oxygen for 12 h and incubated with 21%oxygen for 12 h immediately after the addition of PGC-1αagonist ZLN005).The apoptosis rate,ROS content,mitochondrial membrane potential level and cellular serum IL-10 and IL-18 content,as well as the expression level of cellular pyroptosis-related proteins and the expression level of mitochondrial dynamics-related proteins were detected in each group.The morphologies and structures of cells and mitochondria were observed in each group.Results 1.Compared with the Con group,the Hyp-R group showed increased expression of Caspase-1,Nlrp3,GSDMD-N and Drpl proteins(P<0.05),increased secretion of IL-18 in the cell supernatant,increased late apoptosis,increased ROS content and increased fluorescent content of JC-1 monomers(P<0.05).2.Compared with the Hyp-R group,the expression of cellular pyroptosis-related proteins in the Hyp-R group was reduced,the secretion of IL-18 in the cell supernatant was reduced,the content of ROS was reduced,and the fluorescence content of JC-1 monomer was reduced(P<0.05).3.The mitochondria in the Hyp-R group were swollen,the mitochondrial ridges were lysed,and the cells had the characteristics of partially suspected pyroptosis.The damaged cellular and mitochondrial structures in the Hyp-R+ZLN group were repaired.Conclusion PGC-1αalleviates renal tubular epithelial pyroptosis by regulating mitochondrial biosynthesis,thereby affecting pyroptosis in HK-2 cells.

关 键 词：线粒体 氧化应激 肾皮质近曲小管上皮细胞 细胞焦亡 

分 类 号：R363[医药卫生—病理学]