Role Of Nuclear Factor Kappa B In Pathogenesis Of The Mice With Viral Myocarditis

Viral myocarditis (VMC) is a common cardiovasculardisease. In China, VMC cases have been increasing year afteryear. VMC has become one of the main causes of sudden unknowndeath events in teenagers. Moreover chronic VMC oftenresults in dilated cardio-myopathy. These demonstrate thatVMC has greatly threatened human health. However, up to now,the mechanism of VMC has been unclear, which leads to thelack of effective treatments of VMC. So it has importantlytheoretic and practical significance to illuminate themechanism of VMC.It is known that viral infection is an important pathogenof VMC, and VMC caused by coxsackievirus group B type 3 (CVB3)infection accounts for more than fifty percent VMC cases.Previous studies showed that cytokines play a very complexrole during the process of viral myocarditis,and possessdifferent activity in different period. Most of them can beinduced or inhibited by themselves or others. It is wellknown that indirect immunological injury in VMC isassociated with the infiltration of a great amount ofinflammatory cells. The infiltration of inflammatory cellsis one of characteristic pathological changes in VMC.Generally, the infiltration of inflammatory cells is acomplex and multiple-stepped process involved in many cellsand molecules. Induced by inflammatory signals andcell-adhesion molecules, various inflammatory cellsaccumulate in the site of infection. The process consistsof rolling, adherence, extravasation and so on. It has beenconfirmed that NFκB play a vital role in many cardiovasculardiseases such as artherosclerosis, heart failure,myocardial ischemia-reperfusion. Nora Gorenstudy showedactivation of NFκB in cardiomyocytes has been shown to bean important mediator of the inflammatory response in theheart and of organ damage, According to above, wehypothesized that NFκB may play a vital role in thepathogenesis of myocarditis.Therefore, in this study we first established VMC modelsthrough BALB/c mice infected with coxsackievirus B3, aftervirus inoculation until day 0,4,7,10,we examined (1) thecontents of NFκB in the cadiocyte nucleus.(2) Virus titersof hearts (3) score for myocardial necrosis and cellularinfiltration. Based on the results, we further studied theeffects of CVB3 infection dose, infection time in NFκB ofthe cadiocyte nucleus and score for myocardial necrosis andcellular infiltration, degree of relationship of the in NFκB of the cadiocyte nucleus and score for myocardialnecrosis and cellular infiltration. Our study would providenew theoretic base and experimental evidence for preventionand therapy of VMC. The contents of NFκB in the cadiocytenucleus was detected at the 0,4th,7th and 10th day post CVB3infection quantitatively by the western-blot. The resultsshowed that the contents of NFκB in the cadiocyte nucleusincreased slightly at the forth day post infection, then NFκB was increased continuously, and NFκB was climbed a peakat the10th day post infection. The contents of NFκB at4th,7th and 10th day were 1.51,1.96and 2.28 folds higherthan that of uninfected control(P<0.01). It indicated thatthe contents of NFκB was dependent of the infection timewithin 10 days post infection in myocardial tissue in VMCmice. CVB3 loading in myocardial tissue was analyzed at 0,4th,7th and 10th days post infection. The results showed CVB3infectivity was found (TCID50 was 103.50) at the 4th day postinfection in myocardial tissue, then TCID50 increased at the7th day(104.38), and at 10th day TCID50 reduced to 103.74. Itindicated that CVB3 infection influenced the NFκB inloading-independent manner in vivo. At the same timeanalyzing score for myocardial necrosis and cellularinfiltration, linear correlation analysis showed Virustiters of hearts and myocardial necrosis is positivecorrelation remarkably(r=0.790,0.759) at 7th, 10th day postinfection;the contents of NFκB in the cadiocyte nucleusand myocardial necrosis, cellular infiltration is positivecorrelation remarkably(r=0.985,0.965).In summary, we found that the contents of NFκB in thecardiocyte nucleus was influenced greatly by CVB3 infection,regulation of CVB3 infection on the contents of NFκB in thecardiocyte nucleus was independent of CVB3 replication. Itgives an insight into pathogenesis of VMC. Linearcorrelation analysis showed virus replication in thecardiocyte is important in early phase of pathologicdevelopment, NFκB play a vital role in the regulation ofinflammatory cell infiltrate myocardium and pathogenesis ofmyocarditis. To interfere in activation of NFκB may reducethe aggression to myocardium by Immune effector cell,attenuate inflammatory cell infiltrate myocardium andmyocardial necrosis, sustain its integrity of structure andfunction. The study has elucidated the role of NFκB inpathogenesis of VMC, providing a potential pathway inprevention and therapy of VMC and giving a new idea toresearch on other inflammatory related diseases.