不同时相的氙气预适应对小鼠肾脏缺血再灌注损伤的干预作用.doc

不同时相的氙气预适应对小鼠肾脏缺血再灌注损伤的干预作用 贾平 丁小强 邹建洲 方艺 滕杰 【摘要】 目的 观察不同时间点的氙气预处理对小鼠肾脏缺血再灌注损伤（I/R）的干预作用，并探讨其机制。方法 采用双侧肾蒂夹闭法建立小鼠I/R模型，动物随机分6组：假手术组（sham）、缺血再灌注组（I/R）、2h氙气预处理组（Xe-P2h）、2h氮气预处理组（N2-P2h）、24h氙气预处理组（Xe-P24h）和24h氮气预处理组（N2-P24h），每组6只；氙/氮气预处理组即在肾脏I/R术前2h或24h予70%氙气或70%氮气暴露2h，于肾脏再灌注24h后留取血液、肾脏标本，收集24h尿量，分别检测肾功能、肾组织病理；并采用Western blot法检测单纯氙气预处理后不同时间肾脏缺氧诱导因子1α（HIF-1α）与血管内皮生长因子（VEGF）的表达。结果 与sham组相比较，各实验组小鼠肾脏再灌注24h后Scr、BUN浓度均明显升高(p0.05)，而Xe-P2h组和Xe-P24h组Scr、BUN浓度较I/R组与氮气预处理组显著减低(p0.05)，且以Xe-P24h组降低更为显著。组织学上表现与肾功能改变相一致，即Xe-P2h组和Xe-P24h组肾组织病理损伤较I/R组与氮气预处理组显著减轻，肾小管评分前二组也显著低于后者。另外，单纯氙气预处理呈时间依赖性上调小鼠肾脏HIF-1α及其靶蛋白VEGF的表达。结论 不同时相的氙气预适应均可以减轻小鼠肾脏缺血再灌注损伤，其机制可能是通过上调HIF-1α及其靶基因的表达。 【关键词】氙气；预适应；肾脏缺血再灌注损伤；缺氧诱导因子1α Diverse effect of xenon preconditioning on renal ischemia-reperfusion injury in mice JIA Ping, DING Xiaoqiang, ZOU Jianzhou, FANG Yi, TENG Jie. Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China Corresponding author: TENG Jie. E-mail:  HYPERLINK mailto:teng.jie@ teng.jie@ [Abstract] Objective To investigate the effect of xenon preconditioning with different durations on renal ischemia-reperfusion injury in mice. Methods 36 mice were randomly divided into six groups as follow: sham operation group (sham), renal ischemia-reperfusion injury group (I/R), 2h xenon-pretreatment group (X-P2h), 2h N2-pretreatment group (N-P2h), 24h xenon-pretreatment group (X-P24h) and 24h N2-pretreatment group (N-P24h); I/R was performed by clamping bilateral pedicles for 30 min followed by reperfusion. In xenon or N2 pretreatment groups, mice were exposed for 2 h to either 70% xenon or 70% N2 balanced with 30% oxygen 2h or 24h before the induction of renal IR injury. Blood sample and kidneys were collected 24h after renal IR (n=6). Serum creatinine (Scr) and blood urea nitrogen (BUN) were examined. The kidney tissue was stained by HE. Another 24 mice were divided into two groups: xenon and N2 pretreatment groups, which were only exposed to either 70% xenon or 70% N2 f