高糖腹膜透析液对腹膜间皮细胞PGC-1α蛋白表达以及线粒体相关氧化凋亡的影响  

Effect of high glucose peritoneal dialysis solution on PGC-1α expression and mitochondria related oxidative injury in humanperitoneal mesothelial cells

作　　者：朱雪婧[1] 文枫[1] 杨淡昳[1] 刘静[1] 袁曙光[1] 李军[1] 刘虹[1] 许向青[1] 孙林[1] 刘伏友[1] 

机构地区：[1]中南大学湘雅二医院肾内科,中南大学肾病研究所,肾脏病与血液净化学湖南省重点实验室,长沙410011

出　　处：《中南大学学报（医学版）》2013年第11期1085-1091,共7页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金青年基金(81300600);中南大学自由探索计划课题(2012QNZT146)~~

摘　　要：目的:研究腹膜透析患者腹膜间皮细胞(human peritoneal mesothelial cells,HPMC)中高葡萄糖腹透液(peritoneal dialysis solution,PDS)对细胞线粒体结构与功能、过氧化物酶体增殖物激活受体γ辅助激活因子(peroxisome proliferatoractivated receptor gamma coactivator 1-alpha,PGC-1α)表达、活性氧(reactive oxygen species,ROS)产生的影响,深入探讨高糖PDS环境下HPMC线粒体氧化损伤中的分子机制。方法:体外培养HPMC,用不同葡萄糖浓度PDS(1.5%,2.5%,4.25%)干预。MitoSox荧光染色检测线粒体ROS生成。线粒体呼吸链以及抗氧化物酶活性试验检测线粒体功能。Western印迹检测PGC-1α蛋白的表达。结果:高糖PDS抑制线粒体呼吸链复合物III,抗氧化物酶活性明显下降,并呈浓度依赖性。同时线粒体ROS明显升高,细胞凋亡增多。PGC-1α蛋白的表达随高糖PDS浓度升高而下降。结论:高糖PDS可能通过抑制PGC-1α蛋白的表达,抑制线粒体呼吸链活性以及抗氧化物酶活性,促进ROS积聚,诱导细胞凋亡。Objective：To investigate the mechanism of mitochondrial oxidative injury induced by high glucose peritoneal dialysis solution （PDS） and the protective effect of peroxisome proliferator-activated receptor gamma coactivator 1-alpha （PGC-1α） in the mitochondria of human peritoneal mesothelial cells （HPMC） in the high glucose ambience. Methods：HPMC was cultured in a PDS containing 1.5%, 2.5%and 4.25%glucose for 24 hours. Western blot analysis was used to detect PGC-1αexpression. MitoSOX？Red staining, respiratory chain complexes and antioxidant enzyme activities were determined. Results：The activities of respiratory chain complex III and antioxidant enzymes decreased signiifcantly in a concentration-and time-dependent manner, along with the increased production of mitochondrial reactive oxygen species （ROS） and cellular apoptosis. In addition, protein expression of PGC-1αwas also decreased in the high glucose PDS ambience. Conclusion：High glucose PDS might inhibit PGC-1αexpression, resulting in the inhibition of mitochondrial function and increase of mitochondrial ROS and cellular apoptosis.

关 键 词：腹膜透析 线粒体 氧化损伤 

分 类 号：R692.5[医药卫生—泌尿科学]