STAT3在小鼠急性病毒性心肌炎发病中的作用研究

Role of STAT3 in the pathogenesis of acute viral myocarditis in mice

目的:观察STAT3在小鼠急性病毒性心肌炎(Viral myocartditis,VMC)发病中的作用及其可能作用机制。方法:建立急性VMC小鼠模型,将45只小鼠随机分为3组:正常对照组10只、急性VMC组15只,急性VMC+RPM干预鼠20只,分别采用DMEM和STAT3特异性抑剂RPM0.4mg/kg每日腹腔注射,12d后观察小鼠的一般情况及存活率,心肌组织病理变化,心肌组织病毒滴度,ELISA法检测血清IFN-γ和TNF-α含量。结果:与急性VMC鼠相比,急性VMC+RPM干预鼠一般情况明显加重,心肌组织变性坏死及炎性细胞浸润明显加重,并且血清中IFN-γ和TNF-α含量均增加,但心肌组织病毒滴度两组间无明显差异。结论:STAT3活化在病毒性心肌炎小鼠发病中对心肌组织有一定的保护作用,抑制其活化,小鼠对CVB3的易感性明显增加;STAT3活化虽不能干扰心肌组织中病毒复制,但却可通过抑制IFN-γ、TNF-α的过度表达而对心肌组织有一定保护作用。

Objective：To investigate the role of STAT3 in the pathogenesis of acute viral myocarditis（VCM）in mice and its possible mechanism.Methods：Acute VCM mice models were established forty-five mice were randomly divided into blind control group （n=10）,virus-infection control group（n=15）,RPMintervention group（n=20）.In RPM intervention group,RPM was given to mice intraperitoneally once a day with general dosage of 0.4 mg（/kg·d）at 24 hours before infected with coxsackie virus B3,mice of virus-infection control group were given the same volume of Dulbcco＇s Modifed Eagle Medium and virus.Blind control group was only given the same volume of Dulbcco＇s Modifed Eagle Medium,but not infected coxsackie virus B3.Twelve days later,the general condition and survival rate of mice were observed and then all experimental mice were sacrificed patholog and detecting CVB3 virus titer in myocardium. And double-sandwich ELISA was used to detect the levels of IFN-γ,and TNF-αin the serum.Results：The pathological changes of myocardium of the mice in RPM intervention displayed more seriously than the mice with acute VMC and both the cytokines expressions in the serum of RPM intervention group were higher than those of the acute VMC group,but there was no significant difference in the virus titer between the two groups.Conclusions：The activation of STAT3 can somehow protect myocardial tissues during the incidence of viral myocarditis in mice to inhibit its activation and improve the sensibility of mice to CVB3,although the activation of STAT3 cannot affect CVB3 virus replication,it can inhibit the over-expression of IFN-γand TNF-αto weaken myocardial damage.