The Experimental Research Of Scopolamine Pretreatment On Hepatic Ischemia Reperfusion Injury In Rats

[Objective]This study aimed to build hepatic ischemia reperfusion injury model in rats andto investigate the mechanism of hepatic ischemia reperfusion injury by observing thepathological changes of livers and measuring the level of serum ALT、AST、plasmaXOD、MDA、TNF-、IL-10. The other aim is to investigate the protective effects ofscopolamine pretreatment and its mechanism on hepatic ischemia reperfusion injury.[Methods]Firstly,to build hepatic ischemia reperfusion injury model in rats by Pringle’smethods that block the portal vein,hepatic artery and Common Bile Duct(CBD).SixtySprague Dawley(SD) rats(male) weighing250-350g were devided into3groupsrandomly. Group A,sham operation group,only dissociate the hepatoduodenalligament and the hepatic blood flow was not blocked;Group B,ischemia reperfusiongroup, using Pringle’s methods to build the model of HIRI and blocking time was setto30mins,then recover the hepatic blood flow.Group C,scopolaminegroup,scopolamine injection was injected into the abdominal cavity ofrats(0.006mg/kg) three days before operation continuously.And scopolamine injectionwas injected into sublingual vein(0.006mg/kg)30mins before operation.Each groupwas divided into4subgroups(n=5);T1,hepatic blood blocked30mins and reperfusionfor0mins; T2,hepatic blood blocked30mins and reperfusion for30mins; T3,hepaticblood blocked30mins and reperfusion for60mins; T4,hepatic blood blocked30minsand reperfusion for120mins.The serum level of ALT and AST was measured byAutomatic Chemistry Analyzer(ACA).The content of TNF-、IL-10in plasma wasmeasured by ELISA.The activity of plasma XOD and MDA was detected by colorimetry.The hepatic pathological changes was observed with optical microscope.[Results]1. The level of serum ALT、ASTThe level of serum ALT and AST at T1,T2,T3,T4in group B increasedsignificantly compared with the corresponding time point of group A(p<0.05), and thelevel of ALT and AST in group B rise gradually along with Ischemia Reperfusion timeextended(p<0.05);Compared with group B,the level of ALT、AST decreasedsignificantly in group C(p<0.05).2. The activity of plasma XOD and MDAThe activity of plasma XOD and MDA at each time point in group B increasedsignificantly compared with group A(p<0.05),and the level of XOD and MDA ingroup B rise gradually along with Ischemia Reperfusion timeextended(p<0.05);Compared with group B,the level of plasma XOD and MDAdecreased obviously in group C(p<0.05).3. The content of TNF-in plasmaThe content of plasma TNF-at each time point in group B increasedsignificantly compared with group A(p<0.05),and the level of TNF-in group B risegradually along with Ischemia Reperfusion time extended(p<0.05);Compared withgroup B,the level of plasma TNF-decreased dramatically in group C(p<0.05),butthe level is still higher than group A at each time point(p<0.05).4. The level of plasma IL-10The content of plasma IL-10at time point T2,T3,T4in group B descendedobviously compared with the corresponding time point of group A(p<0.05), at timepoint T1IL-10ascended a little,but there’s no statistic significance compared withgroup A(p>0.05).The level of IL-10in group B decreased gradually along withIschemia Reperfusion time extended(p<0.05);Compared with group B,the level ofIL-10increased obviously in group C(p<0.05).5. Pathological changes of liverThe shape and structure of liver cells is normal in group A;Liver cells edema andsteatosis, hepatic sinusoid were distended,a large number of inflammatory cells(like macrophage,lymphocyte et) infiltrate into liver tissue,and liver cells necrosis can beobserved at each time point in group B;Compared with group B, groupC(scopolamine group) hepatic cells edema,steatosis and necrosis injury was reduceddramatically,little inflammatory cells infiltrated into the liver cells,the histopathologyof liver improved effectively.[Conclusion]1. HIRI can harm liver cells by free radical injury,increasing the synthesis of TNF-and reduce the production of IL-10and so on.2. The pretreatment of scopolamine has protective effects to HIRI in rats,themechanism maybe related to clearing free radicals,reducing lipid peroxidationinjury,stabilizing liver cell biomembrane,suppressing the synthesis ofTNF-,promoting the secretion of IL-10and so on.