Study On The Role Of Jak/Stat Pathway And Interventionaltreatment Of The Extractive Of Hypericum Perforatum L In Myocardialfibrosis Of Mice

Background and objective: Viral myocarditis (VMC) is a commondisease that badly intimidates the health of children, today, thepathogenesis of myocarditis remains unclear, if the patients withmyocarditis is not complete recover, it can develop dilatedcardiomyopathy (DCM), VMC is divided into acute and chronic phase(immune injury period). Myocardial fibrosis is the characteristicpathological changes of viral heart disease (including the acute andchronic myocarditis and part of DCM). The model of experimentalautoimmune myocarditis (EAM) has been induced in susceptible strainsof rats and mice produced by immunization with cardiac myosin (CM), which the pathogenesis is similar with the second phase of VMC(immune injury period). At present, the treatment of myocarditis is notsatisfied with western medicine, and the therapy of traditional Chinesemedicine have a more signigicant effect on myocarditis. Hypericin is themain active ingredient from Hypericum perforatum L. Our preliminarystudy has been reported about Hypericin anti-CVB3induced viralmyocarditis. Now our research results about the effect of the extractiveof Hypericum perforatum L (EHP) on the acute stage of EAM showedthat EHP has therapeutic effect on autoimmune myocarditis, it can notonly inhibit the inflammation degree in autoimmune myocarditis, butalso alleviate the myocardial immune injury. The mechanism of EHPwas related to the inhibition of Perforin/Gram B pathway and improvethe body antioxidant capacity. On this basis, the paper through thepurified porcine CM induced susceptible mice-BALB/C mice toestablish the mice model of myocardial fibrosis in chroninc stage ofEAM. It was aimed at investigating the formation mechanism ofmyocardial fibrosis in chroninc stage of myicarditis, and the therapeuticeffect of EHP on the MF of autoimmune myocarditis, providing newideas and approaches and the experimental basis for the clinicaltreatment of myocardial fibrosis with EHP in myocarditis mice.Methods: BALB/C mice were immunized with porcine cardiacmyosin to establish the model of MF in chroninc stage of EAM, porcine cardiac myosin was injected subcutaneously in the two-sided inguen andthe armpit; the four limbs foot pads to establish MF of EAM. Then allBALB/C mice were randomly divide into normal control group, modelcontrol group, EHP low dose, medium dose and high dose groups,captopril group.The mice were treated by different concentration EHPand captopril every day, and the course of treatment was50days. Afterthe treatment we made pathological section dyeing them with HE andMASSON to observe the Cardiac fibration degree, we detected theexpression level of TNF-α, COL-Ⅰ and COL-Ⅲ by the means ofELISA, and the gene expression of JAK1and STAT3was detected byRT-PCR.Results: After having done the model, the myocatdial fibrosisdegree of Model group was more serious, and the expression level ofTNF-α, COL-Ⅰand COL-Ⅲwas increased obviously; the geneexpression level of JAK1, STAT3was significantly higer than normalcontrol group (p<0.05) in the chronic phase of EAM. And after thetreatment, the medium dose, high dose of EHP and captopril cansignificantly improve the degree of MF, decreased the expression levelof TNF-α, COL-Ⅰand COL-Ⅲ, obviously reduced the JAK/STATpathway JAK1mRNAand STAT3mRNA expression (p<0.05).Conclusion:1.The activation of JAK/STAT signal pathway canincrease the expression of the COL-Ⅰand COL-Ⅲand the pathway may be one of the mechanisms of myocardial fibrosis in EAM chronic phase.2. The extractive of Hypericum perforatum L can restrain myocardialfibrosis by blocking the JAK/STAT signal pathway.