右美托咪定激活PI3K/Akt通路改善LPS诱导的大鼠急性肺损伤实验研究Experimental study of dexmedetomidine activating PI3K/Akt pathway to improve LPS-induced acute lung injury in rats
陈胜阳;张永强;刘俊;刘国泽;田建民;岳修勤;
摘要(Abstract):
目的考察右美托咪定(Dex)对脂多糖(LPS)诱导的大鼠急性肺损伤(ALI)的影响,并探讨可能与PI3K/Akt信号通路改变的相关机制。方法将80只SD大鼠根据建模方法随机分为5组:对照组、模型组、Dex低剂量组、Dex高剂量组、Dex+LY294002组,建模24 h时处死并分离肺组织,观察组织病理切片,检查肺水肿程度及微血管通透性,采用Westernblotting法检测Akt及其磷酸化蛋白以及线粒体凋亡信号相关蛋白的表达水平,检查线粒体细胞色素C、膜电位及ATP含量,并用电镜观察线粒体形态,采用流式细胞术检测肺组织细胞凋亡情况,采用DCFH-DA探针荧光显微镜法检测细胞内的活性氧(ROS)水平。结果 LPS滴注24 h后,病理切片表现有明显的ALI特征,Dex在50μg/kg剂量时可明显改善LPS诱导的ALI病理特征;以对照组为参照,p-Akt(Thr308)与p-Akt(Ser473)的相对表达量模型组未发生明显变化,Dex组则均显著增高(P<0.001),在Dex+LY294002组的表达水平较Dex组显著降低(P<0.001);模型组的Bax与Bcl-2蛋白较对照组的相对表达量分别显著升高与降低(P<0.001),Dex组分别降低与升高至接近对照组水平,Dex+LY294002组又分别回升与回降;对照组、模型组、Dex组、Dex+LY294002组的肺组织细胞凋亡率分别为2.4%、19.5%、6.7%、13.1%;各组的ROS水平变化与肺组织细胞凋亡情况一致性良好。结论 Dex可通过激活PI3K/Akt信号通路减轻LPS诱导的肺组织细胞凋亡及线粒体凋亡信号激活,继而改善ALI,发挥肺保护作用。
关键词(KeyWords): 右美托咪定;急性肺损伤;PI3K/Akt通路;细胞凋亡
基金项目(Foundation): 河南省医学科技攻关计划项目(2018020351)
作者(Author): 陈胜阳;张永强;刘俊;刘国泽;田建民;岳修勤;
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