Preconditioning Effects Of Dexmedetomidine On Hepatic Ischemia Reperfusion Injury In Rats

Background: Liver ischemia reperfusion injury is a major event duringthe perioperative period in many clinical situations including livetransplantation, hepatectomy, resection of hepatic hemangioma andtraumatic hemorrhagic shock.In some severe cases, it can cause liver failure,no function of organ transplants and multiple organ dysfunction syndrome.A large number of research aims to explore the mechanism of live ischemiareperfusion,amony them,the common finding of hepatic inflammation play avital role during a variety of liver diseases including drug-induced livertoxicity, emerging evidence suggests that the adaptive immune system isalso inuenced by the innate immune response leading to live damage. Undernocuity factors,neutrophils and monocytes are activated and generated.Kupffer cells produce TNF-α and IL-1β to lead complement activated, then,induce hepetic apoptosis and necrosis. Inflammatory reaction attack and killexcited hepetic cell and aggrate the tissual injury.Dexmedetomidine is a selective α2adrenoreceptor agonist that has beendescribed as a useful, safe, sedation, analgesia, anti-sympathetic, anti-anxiety,no respiratory depression new drug and has been used in many clinicalapplications. Dexmedetomidine inhabite lipid peroxidation and stess reactioncaused by trauma through the central and peripheral mechanism. It makemore stable hemodynamics, inhabit the immune inflammatory response andthen reduce the damage to the heart, brain, lung, kidney from the injury andhave protection function. Dexmedetomidine reduce the liver injure caused bysepsis, however the role of dexmedetomidine in the pathogenesis of liverI/R injury has not been explored. In the present study, we aimed to study theinfluence of dexmedetomidine in liver I/R in rats through compared ALT,AST, LDH, TNF-α, IL-1β and hepetic apoptosis. Objective:To explore the the role of dexmedetomidine in thepathogenesis of liver I/R injury; To provide new accordance andexperimental date of dexmedetomidine on the clinical application.Methods:27healthy male Wistar rats, randomized to three groups,sham operation(Sham group); liver ischemia reperfusion (I/R group);dexmedetomidine preconditioning(Dex group).No diert12h before the operation, offer enough water.1%pentobarbital sodium (40mg/ml)intraperitoneal injection; put a tube to thecarotid arteries. In Dex group,100ug/kg dexmedetomidine(10ug/ml)intraperitoneally30min before the ischemic insult, in Sham group and I/Rgroup, isodose0.9%Nacl intraperitoneally30min before the ischemicinsult, then do the operation:Sham group: dissociate the hepatis porta, not block blood-supply of thehepatic lobes;I/R group and Dex group: block the portal vein, hepatic artery of thebranching to the right lateral lobe and the median lobe (approximately70%ofthe liver), after30min, reperfusion.In three groups, get blood1ml from the carotid arteries beforeischemia(T1), after reperfusion30min(T2) and after reperfusion120min(T3),centrifugate and get out the serum, Application of automatic biochemicalanalyzer test in each time point in the specimen serum ALT, AST and LDHlevels; Euzymelinked Immunosorbent Assay(ELISA) method was used toexamine the serum TNF-α, IL-1β; Visually study the liver tissue hyperemiasituation after reperfusion120min, then, kill the rat, Flow Cytometry (FCM)method examine the liver cell apoptosis of the liver right lateral lobe and themedian lobe.Results:1Weight, age, operation time, hemorrhage and fluid infusionamong the three group are no significant difference.2The liver tissue hyperemia situation visually after reperfusion120minIn Sham group, liver surface smooth, color is red, size is normal;In I/R group, liver tissure obviously hyperemia, color is dark red, swollen. Compared with the I/R group, the Dex group with liver congestionlevels of light, color is red.3The comparation between the groupsT1: No statistically significant difference among the three groups(P＞0.05).T2: Compared to the Sham group, the expression of ALT, AST, LDH,TNF-α and IL-1β in I/R group was significantly increased, the expression ofALT, AST, TNF-α and IL-1β in Dex group was significantly increased(P＜0.05), the expression of LDH between Dex group and Sham group was notstatistically significant(P>0.05); Compared to the I/R group, expression ofALT, AST, LDH, TNF-α and IL-1β in I/R group was significantlydecreased(P＜0.05).T3: Compared to the Sham group, the expression of ALT, AST, LDH,TNF-α, IL-1β and liver cell apoptosis in I/R group was significantlyincreased, the expression of ALT, AST, TNF-α,IL-1β and liver cellapoptosis in Dex group was significantly increased(P＜0.05), the expressionof LDH between Dex group and Sham group was not statisticallysignificant(P>0.05); Compared to the I/R group, expression of ALT, AST,LDH, TNF-α, IL-1β and liver cell apoptosis in I/R group was significantlydecreased(P＜0.05).4The comparation in each groupIn Sham group: The difference among T1, T2and T3was notstatistically significant(P>0.05).In I/R group: The expression of ALT, AST, LDH, TNF-α and IL-1β inT2and T3was significantly increased as compared to T1(P＜0.05);compared between T2and T3, the difference was not statisticallysignificant(P>0.05).In Dex group: Compared to T1,the expression of ALT, AST, TNF-αand IL-1β in T2and T3was significantly increased(P＜0.05), in T2andT3,the expression of LDH compared with T1was not significantlydifferent(P>0.05); compared between T2and T3, the difference was not statistically significant(P>0.05).Conclusions:Dexmedetomidine preconditioning can decreace theexpression of ALT, AST and LDH in the rat liver I/R, decreace the releaseof the inflammation cytokine TNF-α and IL-1β, reduce the hapatocellularapoptosis caused by liver I/R.