异丙酚通过诱导幼鼠海马神经元线粒体自噬减轻其肝缺血再灌注后脑损伤

目的:探究异丙酚对肝缺血再灌注后幼鼠海马神经元线粒体自噬的影响。方法: C57BL/6两周龄的小鼠40只被随机分成4组（n=10）:假手术组(S组)，肝缺血再灌注组（IR组），异丙酚组（P组），异丙酚+自噬抑制剂3-MA组（3-MA组），除S组仅进行开关腹操作外，其余各组均行缺血60 min，再灌注6h建模。取血组织标本及海马组织标本。ELISA法检测血清中脑损伤标志物神经元特异性烯醇化酶（NSE）和S100β浓度及炎症因子白细胞介素6（IL-6）和肿瘤坏死因子α（TNF-α）的浓度；透射电镜法观察自噬小体和线粒体超微结构；Western blot法检测自噬相关蛋白LC3Ⅱ、Nix及凋亡蛋白Caspase-3的表达水平。结果:（1）脑损伤标志物和炎症因子水平， 3-MA组最高，其次为IR组，P组居中，S组最低（P＜0.05）；（2）自噬小体，P组最多，且线粒体结构较完整，依次为IR和S组，3-MA组自噬最少，线粒体肿胀，分裂最多；（3）LC3Ⅱ、Nix蛋白表达水平同上述线粒体自噬水平一致，Caspase-3与此相反（P＜0.05）。结论:异丙酚可促进肝缺血再灌注后幼鼠海马神经元的线粒体自噬，减轻炎症反应，减少细胞凋亡。

Propofol alleviated brain damage by inducing mitophagy in hippocampal neurons after hepatic ischemia and reperfusion in young mice

Objective: To explore the effects of propofol on hippocampal neurons mitophagy after hepatic ischemia and reperfusion in young mice. Methods: Two-week old C57BL/6 mice were randomly divided into 4 groups (n=10): sham operation group (group S); hepatic ischemia-reperfusion group (group M); propofol group (group P); propofol+ 3-MA group (group 3-MA). Besides the sham group that only had abdominal open and close operations, the rest of the groups underwent 60min ischemia and reperfusion for 6h. Blood samples and brain tissues were collected. ELISA was used to detect brain injury markers: neuron specific enolase (NSE) , S100β and inflammatory factors: interleukin-6 ( IL-6 ) , tumor necrosis factor-alpha ( TNF -α ); transmission electron microscope (TEM) was used to observe the structure of autophagosome and mitochondria; protein LC3 II, Nix, caspase-3 expression levels were assessed by Western blot. Results:(1) Concentrations of brain injury markers and inflammatory factors were highest in group 3-MA, followed by group IR, group P, and group sham (P<0.05); (2) the number of autophagosome was biggest in group P, followed by group IR, group S and group 3-MA; mitochondria structure was relatively unbroken in group S, followed by group P, group IR and group 3-MA; (3) LC3 II and Nix protein expression levels were consistent with TEM results, while caspase-3 was opposite(P<0.05). Conclusion: Propofol can promote hippocampal neurons mitophagy after hepatic ischemia and reperfusion in young mice, and reduce inflammation and cell apoptosis.