Department of Anesthesiology, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
J Surg Res. 2013 Nov;185(1):388-98. doi: 10.1016/j.jss.2013.05.004. Epub 2013 May 24.
It was previously reported that propofol, an intravenously administered hypnotic and anesthetic agent, protects organs from ischemia-reperfusion (I/R) injury. However, the underlying mechanisms are largely unknown. Glycogen synthase kinase 3β (GSK-3β) is known to play an important role in the oxidative stress-induced apoptosis. In this study, we investigated the role of GSK-3β and mitochondrial permeability transition pore (MPTP) in the protective effects of propofol against hepatic I/R injury.
The left and median hepatic artery and the portal vein branches were blocked by no-damage artery clips to create the model of partial ischemia (70%), and liver lobes were subjected to warm ischemia for 30, 60, 90 min, respectively. Reperfusion of 120 min was then initiated by the removal of clamp. The MPTP opening was assessed by measuring mitochondrial large amplitude swelling and mitochondrial membrane potential.
Pretreatment with propofol in conditions of hepatic I/R inhibits the apoptosis of hepatocytes as evidenced by decreased terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. Importantly, propofol suppressed the mitochondrial GSK-3β by promoting or preserving its phosphorylation at Ser9, thus restraining the opening of MPTP and preventing the mitochondrial swell and mitochondrial membrane potential collapse.
Propofol protects liver from I/R injury by sustaining the mitochondrial function, which is possibly involved with the modulation of MPTP and GSK-3β.
先前有报道称，静脉内给予的催眠和麻醉药物异丙酚可保护器官免受缺血再灌注（I/R）损伤。然而，其潜在机制在很大程度上尚不清楚。糖原合成酶激酶 3β（GSK-3β）在氧化应激诱导的细胞凋亡中起着重要作用。在这项研究中，我们研究了 GSK-3β 和线粒体通透性转换孔（MPTP）在异丙酚对肝 I/R 损伤的保护作用中的作用。
通过无损动脉夹阻断左肝动脉和中肝动脉以及门静脉分支来创建部分缺血（70%）模型，并分别使肝叶经历 30、60、90 分钟的热缺血。然后通过去除夹闭来开始 120 分钟的再灌注。通过测量线粒体大振幅肿胀和线粒体膜电位来评估 MPTP 开放。
肝 I/R 条件下的异丙酚预处理通过减少末端脱氧核苷酸转移酶 dUTP 缺口末端标记阳性细胞来抑制肝细胞凋亡。重要的是，异丙酚通过促进或保留其丝氨酸 9 的磷酸化来抑制线粒体 GSK-3β，从而抑制 MPTP 的开放并防止线粒体肿胀和线粒体膜电位崩溃。
异丙酚通过维持线粒体功能来保护肝脏免受 I/R 损伤，这可能涉及 MPTP 和 GSK-3β 的调节。
