雷帕霉素预处理对大鼠肾缺血再灌注诱发肺损伤的影响

摘要

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。%Objective To investigate the effects of rapamycin preconditioning on lung injury in-duced 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 ex-amination 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-αlevels 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-αlevels were decreased,SOD activity was increased and histopathological damage was reduced in group R(P <0.05).Conclusion Ra-pamycin preconditioning can reduce lung injury caused by renal I/R through attenuating oxidative stress and inhibiting inflammatory response in rats.