Li Qingwen, Cui Shanshan, Jing Guoqing, Ding Huang, Xia Zhongyuan, He Xianghu
MD, Department of Anesthesiology, Renmin Hospital of Wuhan University, Hubei, China. Manuscript preparation and writng.
MD, Department of Anesthesiology, Renmin Hospital of Wuhan University, Hubei, China. Conception and design of the study, acquisiton of data.
Acta Cir Bras. 2019 Feb 14;34(1):e20190010000005. doi: 10.1590/s0102-865020190010000005.
To investigate the role of PI3k/Akt signal pathway in the protective effects of propofol on intestinal and lung injury induced by intestinal ischemia/reperfusion(I/R).
Male Sprague-Dawley rats were subjected to 45 min of ischemia by occluding the superior mesenteric artery and to 2h of reperfusion to establish the model of I/R. Twenty four rats were randomly divided into four groups: Sham, intestinal I/R (II/R), propofol (P), wortmannin (W). In groups P, W, propofol was injected intravenously and continuously at the onset of reperfusion via infusion pump. PI3K inhibitor (wortmannin) was administered intravenously in group W 25 min before ischemia. Intestinal tissues and lung tissues were obtained for determination of histologic injury, wet/dry weight ratio, malondialdehyde (MDA) levels, superoxide dismutase (SOD) and myeloperoxidase (MPO) activities. Meanwhile, the expressions of caspase-3 and phosphorylated Akt (p-Akt) in intestines and lungs were detected by western blot.
Propofol treatment alleviated intestinal and lung morphological changes which were observed in II/R group,Moreover, wet/dry weight ratio, the MDA level, MPO activity and expression of caspase-3 were significantly decreased whereas the SOD activity and p-Akt expression were significantly increased. Notably, the protections were significantly reversed by pretreatment of wortmannin.
PI3K/Akt pathway activation play a critical role in the protective effects of propofol on intestinal and lung injury induced by ischemia/reperfusion.
探讨PI3k/Akt信号通路在丙泊酚对肠缺血/再灌注(I/R)诱导的肠和肺损伤的保护作用中的作用。
雄性Sprague-Dawley大鼠通过阻断肠系膜上动脉进行45分钟的缺血,并进行2小时的再灌注以建立I/R模型。24只大鼠随机分为四组:假手术组(Sham)、肠I/R组(II/R)、丙泊酚组(P)、渥曼青霉素组(W)。在P组和W组中,再灌注开始时通过输液泵静脉持续注射丙泊酚。W组在缺血前25分钟静脉注射PI3K抑制剂(渥曼青霉素)。获取肠组织和肺组织以测定组织学损伤、湿/干重比、丙二醛(MDA)水平、超氧化物歧化酶(SOD)和髓过氧化物酶(MPO)活性。同时,通过蛋白质印迹法检测肠和肺中caspase-3和磷酸化Akt(p-Akt)的表达。
丙泊酚治疗减轻了II/R组中观察到的肠和肺形态学变化,此外,湿/干重比、MDA水平、MPO活性和caspase-3表达显著降低,而SOD活性和p-Akt表达显著增加。值得注意的是,渥曼青霉素预处理显著逆转了这些保护作用。
PI3K/Akt通路激活在丙泊酚对缺血/再灌注诱导的肠和肺损伤的保护作用中起关键作用。