Expression And Significance Of Intercellular Adhesion Molecule-1 In Myocardial Of Viral Myocarditis Mice

Viral myocarditis(VMC) is a disease that virus offend the heartdirectly and induce immunity reaction,cardiac muscle necrosis andinterstitium inflammatory cell infiltration.It is a common paediatricscardiovascular disease.The clinical manifestations and the prognosisof VMCare diversification,the severe cases of VMC can inducecongestive heart failure,Aase's syndrome,cardiac shock even suddendeath,some patients gradually change into dilated cardiomyopathyafter relieving from acute stage symptom,all these can severelythreaten the health of patients.The VMC results from many kinds ofvirus.The Coxsackie virus B3 (CVB3)is one of the most commonvirus,this viewpoint has been confirmed not only in the study ofanimal model but also in the clinical research.Since 1970's,the incidence of VMC has become more andmore,andanimal models or cell models of VMC induced byCoxsackieviruses group B(CVB) have been established.Scientistsapproach the athogenesy from immune reaction \apoptosis andetc.,but the pathogenetic has not been explored clearly.One hand, it isrelated with the myocardial damage provoked by virus , the otherhand the Cell-mediated immune reaction is also important.TheCell-mediated immune reaction has been considered predominantrole among the process of myocardial cell damage of VMC ,but theprocess and mechanism of immunologic injury has not beencompletely elucidate.Therefore,exploring the pathogeneticmechanism of VMC and providing theoretical basis for the treatmentis a problem which needs urgently solving.In recent years, the intercellular adhesion molecule(ICAM-1)which acts as a significant cell adhesion molecule related with thecardiovascular disease has paid close attention of the people.somestudy discover that the relation between them is intimited. ICAM-1 isan important role not only in the maintaince of the normalcardiovascular function,but also among the development of somecardiovascular disease.ICAM-1 belongs to a member of immunoglobulin superfamily(IgSF) in the cell adhesion molecules.It is one of the most earlydiscoverable cell adhesion molecule.ICAM-1 generally distributes inthe surface of cells in all kinds of tissues, such as neutrophilicgranulocyte,macrophage,lymph cell,vascularendothelial cell andmyocardial cell and so on,and it produces a marked effect by meansof ligand-receptor corresponding modality.Its main ligand islymphocyte function associated antigen-1(LFA-1).LFA-1 mainlydistributes in the surface of neutrophilic granulocyte,natural killercell(NK),T cell,etc.After ICAM-1and LFA-1 adhere,it may be takeplace many kinds of biological effect:1.it participates in theCell-mediated kill process of cytotoxicityt lymphocyte(CTL) andNK;2.it participates in the function of helper T cell and initiationsantibody response of organism;3.it participates in the cell-mediatedantibody dependent cell mediated cytotoxicity(ADCC) ofneutrophilic granulocyte and lymphomonocyte;4.it participates in theinteraction between the leukomonocyte and the matrixcell.Therefore,ICAM-1 promotes adhesiveness of inflammationlocation and has became a significant role which controls the tumoraggravation and metabasis and adjusts organism immunologicresponse.ICAM-1 showes low level expression in the silent white bloodcorpuscle and endothelial cell,but quickly upregulation on the manytypes cells,such as white blood corpuscle,endothelial cell,cellulaepithelialis,horny cell and desmocyte,when they are under the effectof the inflammation cytokine,such as interferon-γ(INF-γ),lipopolysaccharide(LPS) , interleukin-1β(IL-1β) , tumor necrosisfactor-α(TNF-α),etc.Usually,the expression of ICAM-1 is verysparing on the myocardial cell and it can not be detect with commonimmune methods,but the expression of ICAM-1 can increase manytimes in the some pathological agent stimuli. For example,the lethalheart damage,the heart ischemia-reperfusion,the heart graft rejectivereaction and the effect of cytokines(TNF-α,etc).Overseas research discovers ICAM-1 takes part in the processof myocarditis and damages the cardiac muscle with other cytokinestogether and may be lead to myocardial cell death.ICAM-1 has beenan important role in the development of VMC,but relevant aspectstudies are very few either in the domestic or in the overseas atpresent.ICAM-1 has became a key role in the process of mediating andparticipating in the cardiac muscle cell damage and necrosis,but mostconfines to adult.The study demonstrates that the expressed amountof ICAM-1 in the myocardium of the mice which are infected byCVB3 and happen to cardiac damage is increase and the augmentedextent of its express has been intimate correlation of myocardialdamage extent.This study uses Hela cell in vitro culture toestablishment the model of CVB3 infected Hela cell and progressesvirus amplification and then observe cytopathic effect(CPE) andmeasure 50%tissue infection dose(TCID50).Seventy BALB/c miceare randomly divided into two groups,experimental group andcontrol group.The experimental group is fifty and five and thecontrol group is fifteen.BALB/c mice are inoculated of 100TCID50CVB3.as the experimental group of VMC mice model,but BALB/cmice are injected saline as the control group.All groups mice arekilled at the 7th,14th,21st day.The heart is divided into three partsalong the long axis of leftventricle.one part is proceeded microtomesection in order to observe pathological change of the cardiac muscletissues after HE staining and calculate pathological integral of thecardiac muscle tissues;two part calculates virus titre of the cardiacmuscle tissues,the other part is used to detect content of ICAM-1with enzyme linked immunosorbent assay(ELISA) methodand,compared with control group,and anaylsis the correlationbetween the virus titre and the pathological integral of the cardiacmuscle tissues,between the expressed amount of ICAM-1 and thepathological integral of the cardiac muscle tissues in order to explorethe pathogenetic relation of puerile VMC and find another cure roadof VMC.This will be beneficial to develop novel therapeutic strategyand protect the health of humankind.Resault: (1)Measure CVB3 TCID50=10-6.51.(2)Myocardialpatholog change of VMC mice shows that myocardial cell necrosis isconspicuous,inflammatory cell,mostly lymph cell, infiltrates aroundthem but the cardiac muscle cell lines up in order in the controlgroup.(3)The virus titer in the musculature of the VMC miceobviously increase at 7th day ,begin to decrease at 14th day and itcan not be detected at. 21st day However, the virus titer of thecontrol group is negative at any time.(4)The expression of ICAM-1in the musculature of the VMC mice after inoculated of virus start toincrease at 7th day, reach the peak at 14th day, dectease obviously at21st day, which have obviously difference with the control group.(5)The dependablity analysis between the virus titer and thepathological integral in the the musculature of the VMC micedemonstrate that there is dependablity (r=0.492,P<0.05)at 7th dayand there is no dependablity (r=0.271,P>0.05)at 14th day. Thedependablity analysis between the expression of the the ICAM-1 andthe pathological integral in the the musculature of the VMC micedemonstrate that there is positive correlation,that is r=0.54,P<0.05 at7th day, r=0.61,P<0.01 at 14th day and r=0.495,P<0.05 at 21st day.Conclusion:The positive correlation in the dependablityanalysis between the expression of the ICAM-1 and the pathologicalintegral in the the musculature of the VMC mice demonstrates thatICAM-1 educes an important effect on the developing of the VMC.The result that the expression of the ICAM-1 obviously increases inthe musculature of the VMC mice compared with the control groupand has a close correlation with the damage proceed and severitydegree of musculature shows that ICAM-1 educes an importanteffect on the immunologic injury and it can be as a indicatrix toinfect the level of myocardial cellular necrosis and VMC. The antiadhesion molecule may be become an effective measure for theprotect and the treatment of the VMC.