JAK/STAT信号通路在小鼠心肌梗死发病中的作用及对NF-κB、TNF-α表达的影响

Role of JAK/STAT signaling pathway in pathogenesis of myocardial infarction in mice and its effect on expressions of NF-κB and TNF-α

目的:探究JAK/STAT信号通路在小鼠心肌梗死发病中的作用及对核因子kappaB(NF-κB)、TNF-α表达的影响。方法:选择30只SD健康雄性小鼠,10只为正常组,20只建立心肌梗死模型,并将心肌梗死模型小鼠随机分为心肌梗死组、阻断干预组,对阻断干预组模型小鼠使用AG490溶液进行灌胃处理,正常组与心肌梗死组小鼠使用等量生理盐水进行灌胃处理。对3组小鼠心功能指标以及心脏、左心室重量指数进行检测,Western blot法检测JAK/STAT通路相关蛋白表达,对心肌细胞凋亡情况进行检测,酶联免疫吸附试验检测NF-κB、TNF-α水平。结果:正常组小鼠各项心功能指标水平均低于心肌梗死组和阻断干预组,且阻断干预组小鼠各项心功能指标水平均低于心肌梗死组(P<0.05)。正常组小鼠心脏、左心室重量及心脏、左心室重量指数均低于心肌梗死组和阻断干预组,阻断干预组小鼠心脏、左心室重量及心脏、左心室重量指数均低于心肌梗死组(P<0.05)。正常组小鼠JAK/STAT通路相关蛋白相对表达量均低于心肌梗死组和阻断干预组,且阻断干预组小鼠JAK/STAT通路相关蛋白相对表达量均低于心肌梗死组(P<0.05)。心肌梗死组小鼠各时间点心肌细胞凋亡率均高于正常组,阻断干预组小鼠各时间点心肌细胞凋亡率均低于心肌梗死组,高于正常组(P<0.05)。正常组小鼠心肌组织NF-κB、TNF-α表达水平均低于心肌梗死组和阻断干预组,阻断干预组小鼠心肌组织NF-κB、TNF-α表达水平均低于心肌梗死组(P<0.05)。结论:小鼠心肌梗死发病后心功能及心脏、左心室重量指数出现异常,使用AG490溶液阻断JAK/STAT信号通路后,小鼠心功能及心肌细胞凋亡情况得到改善,心脏、左心室重量指数下降,抑制心肌组织炎症反应。

Objective:To explore the role of JAK/STAT signaling pathway in the pathogenesis of myocardial infarction in mice and its effects on the expressions of nuclear factor kappa B(NF-κB)and TNF-α.Methods:Thirty SD healthy male mice were selected,which 10 cases were in the normal group and the remaining 20 cases were established myocardial infarction model.The myocardial infarction model mice were randomly divided into the myocardial infarction group and the blocking intervention group.The blocking intervention group model mice were treated with AG490 solution by gavage,and the normal group and the myocardial infarction group mice were treated with the same amount of normal saline by gavage.Cardiac function index,cardiac and left ventricular mass index of three groups of mice were detected,JAK/STAT pathway-related protein expression was detected by Western blot,cardiomyocyte apoptosis was detected,and the levels of NF-κB and TNF-αwere detected by enzyme-linked immunosorbent assay.Results:The levels of cardiac function indexes in normal mice were lower than those in myocardial infarction group and blocking intervention group,and the levels of cardiac function indexes in blocking intervention group were lower than those in myocardial infarction group(P<0.05).The weight of heart,left ventricle and the weight index of heart,left ventricle in normal group were lower than those in myocardial infarction group and blocking intervention group,and the weight index of heart,left ventricle and the weight index of heart and left ventricle in blocking intervention group were lower than those in myocardial infarction group(P<0.05).The relative expression of JAK/STAT pathway-related proteins in normal mice was lower than that in myocardial infarction group and blocking intervention group,and the relative expression of JAK/STAT pathway-related proteins in blocking intervention group was lower than that in myocardial infarction group(P<0.05).The apoptotic rate of myocardial cells in the myocardial infarction group was higher than that in the normal group at all time points,and the apoptotic rate of myocardial cells in the intervention group was lower than that in the myocardial infarction group,higher than that in the normal group(P<0.05).The expression levels of NF-κB and TNF-αin myocardial tissue of normal mice were lower than those of myocardial infarction group and blocking intervention group,and the expression levels of NF-κB and TNF-αin myocardial tissue of blocking intervention group were lower than those of myocardial infarction group(P<0.05).Conclusion:After the onset of myocardial infarction in mice,cardiac function and left ventricular mass index are abnormal.After blocking JAK/STAT signaling pathway with AG490 solution,cardiac function and myocardial cell apoptosis are improved,cardiac and left ventricular mass index are decreased,and myocardial inflammation is inhibited.