Expression Of B7-H4in Experimental Autoimmune Myocarditis And The Therapeutic Effect Of B7-H4-Fc Fusion Protein On EAM

Objective:This study intends to construct mouse model of experimental autoimmune myocarditis (EAM) to investigate the expression of B7-H4in the progress of myocarditis and observe the therapeutic effect of B7-H4-Fc fusion protein on EAM through testing the blood、spleen lymphocytes and myocardial tissue of mouse models, on the purpose of providing a new direction of studying mechanism of myocarditis and a new treatment for clinical myocarditis.Methods:120Balb/c mice were randomly divided into control group (24mice) experimental group (48mice) and treatment group (48mice). The mice of experimental group and treatment group were injected with myosin(200ug per mouse) to establish EAM models, and the mice of treatment group were injected with B7-H4-Fc fusion protein (3.75mg/kg) from the first day, once a week, while the mice of control group were injected with complete Freund’s adjuvant and PBS. All the mice were killed separately at the14th、21st、30th and45th day for lymphocyte proliferation assay、ELISA、hematoxylin-eosin staining、immunohistochemical staining and real-time PCR. Results:In experimental group, the inflammation infiltration of heart was most serious at the14th and21st day, then it was gradually relieved with time; the results of ELISA、lymphocyte proliferation assay and real-time PCR were similar to that of the inflammation infiltration of heart, and they were higher than those of the control group (P<0.05); B7-H4protein were only detected in the experimental group, and it was constantly expressed during the whole experiment on the endothelium of heart with myocarditis. In treatment group, the inflammation infiltration of heart was relieved than experimental group, which was most obvious at the14th and21st day; the results of ELISA、lymphocyte proliferation assay and real-time PCR were also reduced, but they were still higher than that of control group; the stainingintensity of B7-H4protein didn’t change obviously than experimental group.Conclusion:B7-H4participates in the progress of EAM, and it may be a new way of studying the mechanism of myocarditis. B7-H4-Fc fusion protein is a new protection factor on EAM, and it may be a new therapeutic method of EAM.