线粒体介导产生的活性氧在血管紧张素Ⅱ诱导的肾脏损害中的作用  

Role of mitochondrial reactive oxygen species in angiotensin Ⅱ-induced renal injury

作　　者：冯苗苗[1] 刘素晓[2] 王小晓[2] 崔琳[2] 谢世阳[2] 沈思[2] 朱明军[2] 王幼平[2] Miao-miao Feng Su-xiao Liu Xiao-xiao Wang Lin Cui Shi-yang Xie Si Shen Ming-jun Zhu You-ping Wang(Clinical Department of Integrated Traditional Chinese and Western Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan 450008, China The First Affiliated Hospital, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan 450000, China)

机构地区：[1]河南中医学院中西医结合临床学科,河南郑州450008 [2]河南中医学院第一附属医院,河南郑州450000

出　　处：《中国现代医学杂志》2017年第2期13-18,共6页China Journal of Modern Medicine

基　　金：国家自然科学基金(No:81170243);河南省科技创新杰出人才项目(No:124200510007);河南省科技攻关计划项目(No:162102410048)

摘　　要：目的利用特异性的线粒体活性氧清除剂mito TEMPO,探讨线粒体介导产生的活性氧(ROS)在血管紧张素Ⅱ(AngⅡ)诱发的肾脏损害中的作用。方法通过miniosmotic pump对小鼠皮下灌注AngⅡ复制AngⅡ依赖型高血压模型,而对照组小鼠仅皮下灌注生理盐水。AngⅡ依赖型高血压小鼠分为AngⅡ组和AngⅡ+mito TEMPO组,分别于皮下注射溶媒和mito TEMPO。实验处理4周后,分别检测小鼠尾动脉收缩压、尿8-异构前列腺素及24 h白蛋白排泄量、肌酐清除率和肾脏中线粒体所产生ROS含量的变化,并同时对肾脏组织病理学的改变进行分析。结果与对照组比较,AngⅡ组小鼠血压升高、尿8-异构前列腺素和白蛋白排泄量增加、肌酐清除率下降,肾脏中肾小球硬化指数、肾小管间质损害程度均增加,并伴有线粒体介导产生ROS水平的升高(P<0.05)。除血压外,mito TEMPO能抑制上述病理性变化,从而减轻AngⅡ所诱发的肾脏损害(P<0.05)。结论在AngⅡ诱发的高血压过程中,特异性的线粒体活性氧清除剂mito TEMPO抑制该过程诱发的肾脏损害,并同时伴有肾脏线粒体ROS产生的下降。因此,上述研究结果提示线粒体介导产生的ROS能够促进AngⅡ诱发的肾脏损害。Objective To clarify the role of mitochondrial reactive oxygen species （ROS） in angiotensin Ⅱ （Ang Ⅱ ）-induced renal injury by use of a specific scavenger of mitochondrial ROS, mitoTEMPO. Methods The mouse model of Ang Ⅱ -dependent hypertension was induced with infusion of Ang Ⅱ via subcutaneous miniosmotic pump, and the sham mice were given with normal saline. The Ang Ⅱ-dependent hypertensive mice were divided into control （Ang Ⅱ ） group and experimental （Ang Ⅱ＋ mitoTEMPO） group, which were subcutaneously administered with solvent and mitoTEMPO, respectively. Tail-cuff systolic blood pressure, and urinary excretion of 8-isoprostane and albumin, creatinine clearance, and the levels of mitochondrlal ROS in the kidneys were assayed, and pathological changes of renal tissues were analyzed after 4 weeks of treatment. Results Compared with the sham mice, Ang Ⅱ infusion led to increased systolic blood pressure and urinary excretion of 8-isoprostane and albumin, decreased creatinine clearance, and enhanced glomerulosclerosis index and renal tubulointerstitial injury （P 〈 0.05）. The resuhs were accompanied by the enhanced mitochondrial ROS production in the kidneys （P 〈 0.05）. However, the treatment with mitoTEMPO alleviated all the above changes except for blood pressure, leading to renal protection （P 〈 0.05）. Conclusions Treatment with a specific scavenger of mitochondrial ROS, mitoTEMPO, can inhibit renal injury during Ang Ⅱ-dependent hypertension, which is associated with the decreased mitochondrial ROS production in the kidneys. Thus, the results suggest that mitochondrial ROS can promote Ang Ⅱ-induced renal injury.

关 键 词：血管紧张素Ⅱ 高血压 肾脏损害 线粒体 活性氧 

分 类 号：R544.1[医药卫生—心血管疾病]