雷帕霉素预处理对大鼠肾缺血再灌注诱发肺损伤的影响

目的探讨雷帕霉素（RPM）预处理对大鼠肾缺血再灌注诱发肺损伤的影响及相关机制。方法采用随机数字表法将60只大鼠分为：假手术组（S组）、肾缺血再灌注组（I/R组）、RPM预处理组（R组）,每组20只。采用右肾切除和左肾缺血45 min行再灌注的方法制备肾缺血再灌注损伤模型。R组缺血前给予RPM（10 mg·kg^-1·d^-1）×3 d,最后1次术前2 h灌胃。再灌注6 h后经心脏采集血样,检测血清SOD活性、MDA、IL-1β、IL-6和TNF-α的水平;取肺组织,光镜下观察肺组织病理学结果,并测定肺组织湿干比重（W/D）。结果与S组比较：其他2组肺W/D、血清MDA、IL-1β、IL-6和TNF-α的水平明显升高（P〈0.05）,SOD活性明显降低（P〈0.05）;与I/R组比较：R组肺W/D、血清MDA、IL-1β、IL-6和TNF-α的水平明显降低,SOD活性明显升高,肺组织病理学损伤明显减轻（均P〈0.05）。结论 RPM预处理可减轻大鼠肾缺血再灌注诱发肺损伤,其机制可能与抗氧化应激和抗炎反应有关。

Effects of Rapamycin Preconditioning on Lung Injury Induced by Renal Ischemia-Reperfusion in Rats

Objective To investigate the effects of rapamycin preconditioning on lung injury induced by renal ischemia-reperfusion（ I / R） in rats and its mechanisms of action. Methods Sixty rats were randomly divided into three groups： sham operation group（ group S）,renal I / R group（ group I / R） and rapamycin preconditioning group（ group R）,with 20 rats in each group. Renal I / R was induced by right nephrectomy and left renal artery occlusion for 45 minutes followed by reperfusion. In group R,rapamycin（ 10 mg·kg·day） was intragastrically administered for 3 days before ischemia（ the last administration was performed 2 hours before operation）. Blood samples were collected after reperfusion for 6 hours to determine the activity of superoxide dismutase（ SOD）,generation of malondialdehyde（ MDA） and levels of interleukin-1β（ IL-1β）,interleukin-6（ IL-6） and tumor necrosis factor-α（ TNF-α）. In addition,1ungs were removed for microscopic examination and for determination of wet / dry lung weight ratio. Results Compared with group S,wet / dry lung weight ratio and serum MDA,IL-1β,IL-6 and TNF-α levels were increased and SOD activity was decreased in both group I / R and group R（ P〈0. 05）. Compared with group I / R,wet / dry lung weight ratio and serum MDA,IL-1β,IL-6 and TNF-α levels were decreased,SOD activity was increased and histopathological damage was reduced in group R（ P〈0. 05）. Conclusion Rapamycin preconditioning can reduce lung injury caused by renal I / R through attenuating oxidative stress and inhibiting inflammatory response in rats.