美托洛尔对大鼠心肌梗死后Th1平衡以及钾通道Kv2.1和KIR2.1表达的调控  

Metoprolol affects changes of potassium channels Kv2.1 and KIR2.1 in rats with myocardial infarction by regulating Th1 balance

作　　者：黄侃 史慧颖 王淑男 霍艳萍 刘灿君 那静涛 HUANG Kan;SHI Hui-Ying;WANG Shu-Nan;HUO Yan-Ping;LIU Can-Jun;NA Jing-Tao(The Second Department of Cardiovascular Medicine,the Third Affiliated Hospital of Qiqihar Medical University,Qiqihar 161000,China)

机构地区：[1]齐齐哈尔医学院附属第三医院心血管二科,齐齐哈尔161000 [2]齐齐哈尔卫生学校药理学教研室,齐齐哈尔161000

出　　处：《中国免疫学杂志》2020年第10期1173-1179,1184,共8页Chinese Journal of Immunology

基　　金：齐齐哈尔科技局社会发展公关项目(SFGG-201518)资助。

摘　　要：目的:探究美托洛尔对心肌梗死(MI)大鼠的保护作用,并初步探究其可能的作用机制。方法:将大鼠随机分为假手术组(Sham)、模型组(MI)、美托洛尔低、中、高剂量组(L-metoprolol、M-metoprolol、H-metoprolol)。血液动力学检测大鼠心室功能;TTC染色法检测心肌梗死面积;酶联免疫法检测血清中IFN-γ、IL-2、IL-4、IL-10水平,流式细胞术Th1/Th2细胞比率;蛋白免疫印迹法检测T-bet、GATA-3、Kv2.1、KIR2.1蛋白表达。结果:与Sham组相比,MI组大鼠LVEDD、LVESD显著升高,LVEF、SV、FS显著降低,MAP、LVSP、+dp/dtmax降低,LVEDP、-dp/dtmax显著升高,心肌梗死面积比例升高,血清IFN-γ、IL-2水平升高,IL-4、IL-10水平降低,Th1细胞比率升高,Th2细胞比率降低,Th1/Th2比值升高,T-bet蛋白表达升高,GATA-3蛋白表达降低,Kv2.1、KIR2.1蛋白表达降低,差异均有统计学意义(P<0.05)。与MI组相比,美托洛尔低、中、高剂量组LVEDD、LVESD显著降低,LVEF、SV、FS显著升高,MAP、LVSP、+dp/dtmax升高,LVEDP、-dp/dtmax降低,心肌梗死面积比例降低,血清IFN-γ、IL-2水平降低,IL-4、IL-10水平升高,Th1细胞比率降低,Th2细胞比率升高,Th1/Th2比值降低,脾脏、心肌组织T-bet蛋白表达降低,GATA-3蛋白表达升高,Kv2.1、KIR2.1蛋白表达升高,差异均有统计学意义(P<0.05)。结论:美托洛尔可降低MI大鼠梗死情况,保护大鼠心功能,这可能是通过恢复Th1/Th2平衡,延迟整流钾电流,上调钾通道Kv2.1和KIR2.1蛋白表达实现的。Objective:To explore the protective effect of metoprolol on myocardial infarction(MI) rats and its possible mechanism.Methods:Rats were randomly divided into sham group(Sham),model group(MI) and low,medium,high dose metoprolol group(L-metoprolol,M-metoprolol,H-metoprolol).The ventricular function was measured by hemodynamics;the area of myocardial infarction was measured by TTC staining;levels of IFN-γ,IL-2,IL-4 and IL-10 were detected by ELISA,flow cytometry was used to detect the Th1/Th2 in spleen lymph fluid;the expressions of T-bet,GATA-3,Kv2.1 and KIR2.1 were detected by Western blot.Results:Compared with Sham group,in MI group,the LVEDD and LVESD increased significantly,while LVEF,SV and FS decreased significantly,MAP,LVSP,+dp/dtmax decreased,LVEDP,-dp/dtmax increased significantly,the volume ratio of myocardial infarction increased,levels of serum IFN-γ and IL-2 increased,the levels of IL-4 and IL-10 decreased,Th1 cell ratio increased,Th2 cell ratio decreased,Th1/Th2 value increased,the expression of T-bet protein increased,the expression of GATA-3 protein decreased,the expressions of Kv2.1 and KIR2.1 proteins decreased,the differences were statistically significant(P<0.05).Compared with MI group,in metoprolol group,the LVEDD and LVESD decreased significantly,while LVEF,SV and FS increased significantly;MAP,LVSP,+dp/dtmax increased,LVEDP,-dp/dtmax decreased,volume ratio of myocardial infarction decreased,the levels of serum IFN-γ and IL-2 decreased,the levels of IL-4 and IL-10 increased,Th1 cell ratio decreased,Th2 cell ratio increased,Th1/Th2 value decreased,the expression of T-bet protein in myocardium and spleen decreased,the expression of GATA-3 protein increased,expressions of Kv2.1 and KIR2.1 proteins increased,the differences were statistically significant(P<0.05).Conclusion:Metoprolol can reduce infarction condition of MI rat and protect cardiac function,which may be achieved by restoring Th1/Th2 balance,delaying rectifier potassium current and up-regulating the expressions of Kv2.1 and KIR2.1 p

关 键 词：心肌梗死 美托洛尔 辅助性T细胞 钾离子通道蛋白 机制研究 

分 类 号：R972[医药卫生—药品]