Effects Of Propofol On Brain Injury Induced By Hepatic Ischemia And Reperfusion In Young Mice

Objective: To evaluate the effects of propofol on hippocampal injury induced by hepatic ischemia-reperfusion(HIR)and the role of mitophagy in this process.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 IR);propofol group(group P);propofol+ 3-MA group(group 3-MA).A 70% model of hepatic reperfusion injury was prepared by co-drying the left hepatic lobe and middle vascular(portal,arterial and biliary).Besides the sham group which only carried out abdominal open and close operations,the rest of the groups underwent 60 min ischemia and reperfusion for 6h.IR group prepared 70% hepatic reperfusion injury model according to the above method,group P was injected intraperitoneally Propofol 30 mg/kg 30 min before modeling;3-MA group was injected with 3-MA 5mg/kg 1 hour before model establishment,and intraperitoneal injection of propofol 50μg/kg 30 minutes later;In the S and IR groups,the same amount of emulsifier was intraperitoneally injected 30 min before laparotomy.Blood samples and brain tissues were collected.ELISA was used to detect brain injury markers: neuron specific enolase(NSE),S100β;malondialdehyde(MDA)content(using thiobarbituric acid method)and superoxide dismutase(SOD)activity(by xanthine oxidase method);Immunohistochemistry was used to detect the activation of microglia in hippocampus of each group.Cell apoptosis was assessed by TUNEL and apoptosis index(AI)was calculated transmission electron microscope(TEM)was used to observe the structure of autophagosome and mitochondria;protein LC3 II/I,Nix,p62 expression levels were assessed by Western blot.Results: Compared with the S group,the NSE and S-100β levels of brain damage markers increased in the other groups,MDA content,the activation of microglia and AI in hippocampus increased,SOD activity decreased,LC3 II/I,BNIP3 L/NIX protein content were increased,with the decrease of p62 protein content(P<0.05).Compared with the IR group,the levels of NSE and S-100βin the P group decreased significantly,the MDA content in the hippocampus decreased,while the SOD activity increased,the activation of microglia and AI decreased,and the LC3 II/I,BNIP3L/ NIX protein content increased further with the further decrease of p62 protein content,the NSE and S-100β levels of brain damage markers increased in the 3-MA group,MDA content,the activation of microglia and AI in hippocampus also increased,while SOD activity decreased,LC3 II/I,BNIP3 L/NIX protein content were increased,with the decrease of p62 protein content(P<0.05).TEM observation showed that the mitochondrial structure of the hippocampal CA3 region was complete and the mitophagy was less in S group.Compared with the S group,the number of mitochondria in the IR group,the P group,and the 3-MA group were decreased,and the mitochondrial morphological structure was disordered,the mitochondrial swelling and the autophagic corpuscle increased.Compared with the IR group,the number of mitochondria in the P group increased.The mitochondrial structure was relatively complete,and the number of mitochondrial autophagosomes increased,the number of mitochondria in the 3-MA group decreased,and mitochondrial structure was disordered badly,and the number of mitochondrial autophagosomes decreased.Conclusion: 1.Propofol can alleviate oxidative stress and apoptosis in hippocampus after hepatic ischemia-reperfusion in young mice.2.The mechanism of propofol attenuating hippocampal injury after hepatic ischemia-reperfusion in young rats is related to the activation of mitophagy.