粉防己碱改善心肌梗死大鼠心功能的作用及机制

Effect of tetrandrine on cardiac function in rats with myocardial infarction and its mechanism

目的探讨粉防己碱改善心肌梗死大鼠心功能的作用及潜在机制。方法将48只雄性SD大鼠按随机数字表法分成正常组、假手术组、心肌梗死组、心肌梗死+粉防己碱低剂量(10 mg/kg)组、心肌梗死+粉防己碱中剂量(50 mg/kg)组、心肌梗死+粉防己碱高剂量(80 mg/kg)组,每组8只。采用永久结扎左冠状动脉方法建立心肌梗死模型。利用超声心动图评估大鼠心脏功能[包括左室舒张末期内径(LVIDd)、收缩末期内径(LVIDs)、射血分数(EF)、左室短轴缩短率(FS)],ELISA法检测大鼠血清乳酸盐脱氢酶(LDH)、磷酸肌酸激酶同工酶(CK-MB)水平,Masson染色法测定心肌组织纤维化面积百分比,Western blot、RT-qPCR法分别检测心肌组织B淋巴细胞瘤-2(Bcl-2)、BCL2-Associated X的蛋白质(Bax)蛋白及mRNA相对表达量。结果与假手术组相比,心肌梗死组大鼠的LVIDd、LVIDs,血清LDH、CK-MB水平,心肌组织纤维化面积百分比,心肌组织Bax蛋白及mRNA相对表达量均明显升高(均P<0.05);EF、FS,心肌组织Bcl-2蛋白及mRNA相对表达量均明显降低(均P<0.05)。与心肌梗死组相比,心肌梗死+粉防己碱高、中剂量组大鼠血清LDH、CK-MB水平明显降低(均P<0.05);心肌梗死+粉防己碱高、中、低剂量组大鼠的LVIDd、LVIDs,心肌组织纤维化面积百分比,心肌组织Bax蛋白及mRNA相对表达量均明显降低(均P<0.05);而EF、FS,Bcl-2蛋白及mRNA相对表达量均明显升高(均P<0.05)。结论粉防己碱能改善心肌梗死大鼠的心室重塑和心肌细胞凋亡,其潜在的机制可能与Bax/Bcl-2有关。

Objective To investigate the effect and potential mechanism of tetrandrine on ventricular remodeling and myocardial cell apoptosis in myocardial infarction rats.Methods Forty-eight male AD rats were randomly divided into normal group,sham group,myocardial infarction group,myocardial infarction+tetrandrine low dose group(10 mg/kg),myocardial infarction+tetrandrine mid-dose group(50 mg/kg),myocardial infarction+tetrandrine high-dose group(80 mg/kg)with 8 in each group.The myocardial infarction model was established by permanently ligating the left coronary artery in rats.Echocardiography was used to evaluate the cardiac function of rats,including LVIDd,LVIDs,EF and FS.Serum lactate dehydrogenase(LDH)and creatine kinase-MB(CK-MB)levels were detected by enzyme-linked immunosorbent assay(ELISA).Masson staining was used to measure the fibrosis area of myocardial tissue.By real-time quantitative polymerase chain reaction(RT-qPCR)and Western blot,the expression levels of Bax and Bcl-2 in myocardial tissue were detected.Results Compared with the sham operation group,the LVIDd,LVIDs,serum LDH,CK-MB levels,myocardial tissue fibrosis area,myocardial tissue Bax protein and mRNA relative expression were significantly increased in myocardial infarction group(all P<0.05),and EF,FS,relative expression of Bcl-2 protein and mRNA were significantly reduced in myocardial tissues(all P<0.05).Compared with the myocardial infarction group,the serum LDH and CK-MB levels were significantly lower in the myocardial infarction+high tetrandrine group and the middle-dose group(all P<0.05).LVIDd,LVIDs,percentage of myocardial tissue fibrosis area,the relative expression of Bax protein and mRNA in myocardial tissues were significantly decreased in the myocardial infarction+high,medium and low dose group(all P<0.05),the EF,FS,relative expression levels of Bcl-2 protein and mRNA were significantly increased(all P<0.05).Conclusion Our study indicates that tetrandrine can improve ventricular remodeling and attenuate cardiomyocyte apoptosis in a rat model of myocardial infarction,which is associated with regulating Bax/Bcl-2 protein and mRNA expression.