中文摘要：

目的 探讨七氟烷预处理对大鼠肺缺血再灌注损伤（ischemia-reperfusion injury,IRI）肺组织中细胞自噬的影响。方法 健康成年雄性SD大鼠75只,采用开胸夹闭左肺门建立IRI模型,将75只大鼠编号后按随机数字表法分为5组：假手术组（Sham）,缺血再灌注组（I/R）,七氟烷预处理组（SEVO）,LY294002组（LY）及七氟烷预处理＋LY294002组（PI3K抑制剂）（SEVO＋LY）,各15只。缺血1 h,再灌注120 min后处死各组大鼠,取出肺组织,检测大鼠肺组织湿/干重比（W/D）,Western blot法测定肺组织Beclin-1、LC3Ⅱ/Ⅰ、P62及p-PI3K表达。结果 与Sham组比较,I/R组肺组织发生严重水肿（P〈0.05）,且肺组织细胞自噬水平增加,自噬相关蛋白Beclin-1、LC3Ⅱ/Ⅰ、P62蛋白表达上调（P〈0.05）;与I/R组比较,SEVO组肺水肿明显减轻（P〈0.05）,Beclin-1、LC3Ⅱ/Ⅰ、P62蛋白表达下调,而p-PI3K表达增加（P〈0.05）,LY组与I/R组比较差异没有统计学意义（P〉0.05）;与SEVO组比较,SEVO＋LY组中肺水肿明显加重,Beclin-1、LC3Ⅱ/Ⅰ、P62蛋白表达上调而p-PI3K表达下调（P〈0.05）。结论 七氟烷预处理通过激活PI3K信号转导通路,恢复LIRI期间细胞自噬流,减少自噬性细胞死亡从而对肺缺血再灌注损伤起保护作用。

英文摘要：

Objective To determine the effects of sevoflurane preconditioning on function of autophagy in lung ischemia-reperfusion（I/R） injury in rats. Methods A lung I/R injury model in rats was established by clamping of the left hilum after thoracotomy. A total of 75 healthy adult male Sprague-Dawley （SD） rats （ SPF grade ） were randomly divided into 5 groups （ n = 15 ） ： sham operation group （ Sham ） , ischemia-reperfusion group （ I/R ）, sevoflurane preconditioning group （ SEVO ）, LY294002 （ LY, PI3 K inhibitor） group, sevoflurane preconditioning ＋ LY294002 group （SEVO ＋ LY）. After 1 h of ischemia and 120 rain of reperfusion, the rats were executed and the left lung tissue were harvested for wet-dry weight （W/D） measurement. Western blotting was used to detect the expression of Beclin-1, LC3 Ⅱ/Ⅰ , P62 and p-PI3K. Results Compared with the Sham group, I/R group developed severe lung edema （P 〈 0. 05） ,and had increased level of autophagy and its related protein expression of Beclin-1, LC3 Ⅱ / Ⅰ , P62 （ P 〈 0. 05 ）. The pulmonary injury and increased protein expression found in I/R group were significantly reduced in SEVO group （P 〈0.05）. Only p-PI3K expression was significantly increased in the SEVO group than the I/R group （ P 〈 0. 05 ）. There were no significant differences between LY group and I/R group in these respects （P 〉 0.05 ）. In SEVO ＋ LY group, pulmonary injury was aggravated. The expression of Beclin-1, LC3 Ⅱ/Ⅰ P62 was up-regulated and p-PI3K level was remarkably decreased compared with SEVO group （P 〈0. 05 ）. Gonclusion The results demonstrated that autophagy was involved in the lung I/R pathophysiological process. Sevoflurane preconditioning can protect the lung I/R injury in rats, which is likely related to activation of PI3K signaling transduction and restoration of autophagic flux, at last reducing autophagic cell death.