Opioid Precondition Attenuates Hepatic Ischemia Reperfusion Injury Via Vagus Nerve

BackgroundHepatic ischemia-reperfusion(IR)injury occurs in mounts of clinical settings,which can not be avoided and usually be the cause of postoperative liver failure.With the partial resection of liver,liver transplantation and other surgery in the increasingly popular clinical,liver ischemia-reperfusion injury has become a clinical problem to be solved Opioid receptor precondition were widely studied.Among them,Remifentanil which is widely used opioid receptor agonist in clinic,has suggested that it could protect rats from liver ischemia reperfusion.but current studies can not totally explain how and through which remifentanil acts.As part of autonomic nerves system,vagus nerve directly link brain and liver from the anatomical point of view and mediate interactions between the two.Pervious observations have showed activated vagus nerve reduced systemic inflammation Meanwhile,vagus nerve stim?lation reduces hepatic injury induced by different diseases.As an opioid receptor agonist,remifentanil can activate m?ltiple signaling pathways in the CNS,the objective of our study was to determine whether the central nerve is involved in the effect of remifentanil's protection during hepatic ischemia reperfusion injury in rats.Methods1 ? the model of segmental(70%)ischemia-reperfusion in rats were used,intraperitoneal administration of different concentrations of methyl bromide naltrexone(MNTX)which can not go through the blood-brain barrier as a m? opioid receptor antagonist to antagonize the peripheral m? opioid receptor before opioid agonist precondition.Compare the changes in serum enzyme,histology and the amount of apoptotic cells in each group after hepatic ischemia reperfusion,so as to study the effect of central opioid receptor activation on hepatic ischemia-reperfusion2?With selective hepatic vagotomy surgery in prior,opioid agonist precondition after blocking the vagus nerve,compared the effect of opioid precondition on liver ischemia and reperfusion injury through the changes in serum enzyme,histology and the amount of apoptotic cells in each group.3?The effects of opioid agonists on hepatic ischemia-reperfusion injury were observed by direct administration of opioid receptor agonist as precondition in nucleus DVC in experimental group and control group.And repeated selective hepatic vagotomy in rats to verify the association between DVC and the vagus nerve.Results1 ? Given methyl bromide naltrexone intraperitoneally before opioid agonist precondition,compared to the control group,the serum aminotransferase decreased as well as the amount of necrosis hepatocyte and apoptosis,serum concentration of proinflammatory cytokines is reduced in the experimental groups.2? After the hepatic selective vagotomy,the group which is pretreated by opioid agonist and control group share the similar serum transaminase,the amount of necrosis hepatocyte and apoptosis as well as serum concentration of proinflammatory cytokines are of no difference.3 ? DVC directly given opioid agonist precondition before hepatic ischemia reperfusion,the rat serum aminotransferase were decreased and the damage of the liver was reduced.But the protective effect can be reversed by selective hepatic vagotomy ConclusionOpioid agonist precondition confers the protective effects on hepatic ischemia-reperfusion,and this protective effect is mediated by opioid-activated central neurons through the vagus nerve.