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Effect Of Aminoguanidine On The Expression Of Heme Oxygenase-1 In Acute Cardiac Rejection Of Rat Heart Transplantation

Posted on:2006-06-26Degree:MasterType:Thesis
Country:ChinaCandidate:X G ShiFull Text:PDF
GTID:2144360155969413Subject:Surgery
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Objectives: Heme oxygenase-1 is an enzyme which play an important role in acute rejection and apoptosis. It is one kind of heat shock protein. It has relationship with many circadian and pathologic process because of its catalysis.Its function in heart and blood vessel system is be particular paid attention to. Heavy mental,heme,stress,low oxygen and many other factors can induce the expression of HO-1.Some research indicate that the expression of HO-1 is upgraded by many pathology factors,and the high expression can protect the graft cardiac muscle.But its mechanism is not quite sure.In the ischemia-reperfusionmodel of rats, Aminoguanidine(inhibitor of inducible nitric oxide synthase )can descend the expression of HO-1 in liver and brain tissue,this instructs that iNOS can induce the expression of HO-1.With Ono's rat heterotopic heart transplantation model,we treat rats which have been transplanted hearts with AG ,acut cardiac rejection is observed and the expression of HO-1 and the iNOS activity of grafts are also examined by the method of immunohistochemistry.The purpose is to discuss the expression of HO-1 in rat acute cardiac graft rejection and its relationship with acute rejection ,the relationship between the expression of iNOS and HO-1,and analyse the mechanism of high expression of HO-1.Methods:48 Wistar and 48 SD adult healthy clean inbred strain closed clone rats were chosen.the range of their weight was between 250 and 320g.A rat heterotopic cardiac transplant model with SD donors was used.Group A:SD to Wistar rat heart transplantation ,treated with NS lml peritoneum daily;Group B: SD to Wistar rat heart transplantation ,treated with AG(400mg/kg) injection peritoneum daily; Group C: SD to Wistar rat heart transplantation ,treated with AG(800mg/kg) injection peritoneum daily;In each group 8 transplanted hearts were harvested on fourth day after transplantation,The expression of HO-1 and iNOS activity were detected ,histological grade of acuterejection was also examined.The living days of rest of rats ' heart wereobserved.Statistical analysis:SPSS 10.0 was used to analyze the data.The result was expressed by (x ±s). P<0.05 was considered as statistical significant. Results: l.Histopathological change of transplanted heart:The histopathological change of transplanted heart muscle usually appear at the epicardium at first,then the change will also be found at endocardium. In group A ,the transplanted cardiac muscle was severely damaged four days after the transplant operation,lots of monocytes and metamorphic or necrotic cardiac muscle were found.Hemorrhage was also found in cardiac muscle.ln group B ,the damage change was much less than in group A,and there were significant stastistical differenced between the two groups(P<0.05).In group C,the condition was better than in group B,only few lymphocytes were found in cardiac tissue,there was no obvious cardiac muscle necrosis.Compared with group A and group B,there was also significant statistical differences(P<0.05). 2.INOS activity in each groupThe iNOS activity in group A was the highest.Group B had thelowest iNOS activity.There were statistic difference between eachgroup(P<0.05).3.The expression of HO-1 in each groupThe HO-1 was strongly expressed in group A four days after thetransplantation.The expression mainly located in lymphocytes ofepicadium and endocardium . In some cardiac muscle cells ,HO-1 wasstrongly expressed too.The brown or yellow positive matter located incytoplasm.In group B and group C, the expression were lower than ingroup A,and there was statistic difference(P<0.05).4. The survival days in each groupThe mean survival time in group A was 5.88+0.83 days (n=8) ,ingroup B was 7.88+0.99 days(n=8),group C get the longest survival timewhich was 9.25+1.04 days (n=8) .Conclusions:1.Characteristics of cardiac tissue pathology change during acute graftrejection after rat heart transplatation include:lymphocyte and monocyteinfiltration,myocardium necrosis, Which can be relieved by TreatmentwithAG2.The expression of HO-1 can be greatly induced by rat heart transplantation during acute rejection .Which can be relieved by AQthat indicates iNOS can induce the expression of HO-1.3.AG can prolong the survival time of transplanted hearts.The study indicates that the HO-1 expression has close relationship with acute rejection.AG can weaken the expression by inhabiting the ability of iNOS.
Keywords/Search Tags:rat, heart transplantation, acute rejection, inducible nitric nitric oxide syathase(iNOS), heme oxygenase-1, Aminoguanidine
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