苦参碱对心肌梗死大鼠辅助性T细胞1/辅助性T细胞2平衡及钾通道Kv2.1和KIR2.1的影响

目的探讨苦参碱对心肌梗死大鼠辅助性T细胞1(Th1)/辅助性T细胞2(Th2)平衡及钾通道Kv2.1、KIR2.1的影响。方法制备心肌梗死大鼠模型60只,随机分为模型组、低剂量苦参碱组(50 mg/kg)、中剂量苦参碱组(100 mg/kg)、高剂量苦参碱组(200 mg/kg)、硫氮卓酮组(2.61 mg/kg),每组各12只,药物处理组大鼠于建模成功后每天灌胃治疗,持续7 d,另取12只大鼠作为假手术组。末次给药24 h后处死大鼠检测心肌梗死面积,采用酶联免疫吸附试验(ELISA)检测血清肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白I(cTnI)、干扰素γ(IFN-γ)、白细胞介素(IL)-2、IL-4、IL-10水平,流式细胞术检测外周血Th1/Th2比值,蛋白质印迹法(Western blot)检测心肌组织钾通道Kv2.1、KIR2.1蛋白水平。结果与假手术组比较,模型组大鼠心肌梗死面积比例、血清CK-MB、cTnI、IFN-γ、IL-2水平、外周血Th1/Th2比值升高,血清IL-4、IL-10、心肌组织钾通道Kv2.1及KIR2.1蛋白水平降低(P<0.05);与模型组比较,各药物处理组大鼠心肌梗死面积比例、血清CK-MB、cTnI、IFN-γ、IL-2水平、外周血Th1/Th2比值降低,血清IL-4、IL-10水平、心肌组织钾通道Kv2.1及KIR2.1蛋白水平升高且各苦参碱组呈剂量依赖性(P<0.05);高剂量苦参碱组和硫氮卓酮组大鼠上述指标比较差异均无统计学意义(P>0.05)。结论苦参碱可恢复心肌梗死大鼠Th1/Th2平衡,上调心肌组织钾通道Kv2.1和KIR2.1蛋白的表达,降低心肌梗死面积,起心肌保护作用。

Effects of matrine on helper T cell 1/helper T cell 2 balance and potassium channels Kv2.1 and KIR2.1 in rats with myocardial infarction

Objective To explore the effects of matrine on helper T cell 1(Th1)/helper T cell 2(Th2)balance and potassium channel Kv2.1,KIR2.1 in rats with myocardial infarction.Methods Sixty rats with myocardial infarction were randomly divided into model group,low dose matrine group(50 mg/kg),medium dose matrine group(100 mg/kg),high dose matrine group(200 mg/kg)and thiazolidone group(2.61 mg/kg),with 12 rats in each group.Rats in drug treatment groups were given intragastric administration for 7 d after successful modeling.Another 12 rats were taken as sham-operated group.Rats were killed 24 h after the last administration and myocardial infarct area was measured.Levels of serum creatine kinase isoenzymes(CK-MB),cardiac troponin I(cTnI),interferonγ(IFN-γ),interleukin(IL)-2,IL-4 and IL-10 were measured by enzyme-linked immunosorbent assay(ELISA).Th1/Th2 value in peripheral blood was detected by flow cytometry.Western blotting was used to detect the levels of potassium channel Kv2.1 and KIR2.1 protein in myocardial tissue.Results Compared with sham-operated group,proportion of myocardial infarct area,levels of serum CK-MB,cTnI,IFN-γ,IL-2 and Th1/Th2 value in peripheral blood in model group increased significantly,while levels of serum IL-4,IL-10,potassium channel Kv2.1 and KIR2.1 protein in myocardial tissue in model group decreased significantly(P<0.05).Compared with model group,proportion of myocardial infarction area,levels of serum CK-MB,cTnI,IFN-γ,IL-2 and Th1/Th2 value in peripheral blood in different drug treatment groups decreased significantly,while the levels of serum IL-4,IL-10,potassium channel Kv2.1 and KIR2.1 protein in myocardial tissue increased significantly,and there was a dose-dependent manner in different matrine groups(P<0.05).There were no significant differences of above indexes between high dose matrine group and thiazephone group(P>0.05).Conclusion Matrine can restore Th1/Th2 balance in rats with myocardial infarction,up-regulate the expressions of potassium channel Kv2.1 and KIR2.1 protein in myocardial tissue,reduce myocardial infarction area,and play a role in myocardial protection.