电针对心肌梗死后小鼠长期生存率的影响及其机制研究

Electroacupuncture improves long-term survival of myocardial infarction mice by promoting myocardial angiogenesis and inhibiting ventricular remodeling

目的:探讨电针通过促进血管新生和抑制心室重构提高心肌梗死后小鼠长期生存率的作用机制。方法:雄性C57BL/6小鼠随机分为假手术组、模型组、电针组,每组34只。采用永久性结扎左冠状动脉前降支法复制心肌梗死小鼠模型。造模3 d后电针组给予双侧“内关”“郄门”电针治疗,每日1次,每次30 min,持续28 d。记录各组小鼠从干预开始至140 d的存活情况;检测干预28 d后各组小鼠左心室射血分数(EF);Masson染色法、小麦胚芽凝集素染色法、免疫组织化学法分别检测各组小鼠心肌胶原容积分数、左心室壁厚度、心肌肥大程度及血管新生面积百分比;干预7 d后以Western blot法检测各组小鼠心肌梗死边缘区组织的血管生长因子(VEGF)、缺氧诱导因子(HIF)-1α蛋白表达水平。结果:与假手术组比较,模型组小鼠生存率、EF、左心室壁厚度明显降低(P<0.01),心肌胶原容积分数、心肌细胞横截面积、血管新生面积百分比及VEGF和HIF-1α蛋白表达明显升高(P<0.01)。与模型组比较,电针组小鼠生存率、EF、左心室壁厚度、血管新生面积百分比及VEGF和HIF-1α蛋白表达水平明显升高(P<0.05,P<0.01),心肌胶原容积分数、心肌细胞横截面积明显降低(P<0.01,P<0.05)。结论:电针可以显著改善心肌梗死后小鼠心功能,提高小鼠长期生存率,其作用机制可能与上调HIF-1α、VEGF表达,促进血管新生和抑制心室重构相关。

Objective To investigate the mechanism of electroacupuncture(EA)in improving the long-term survival rate of mice after myocardial infarction by promoting angiogenesis and inhibiting ventricular remodeling.Methods A total of 102 male C57 BL/6 mice were randomly divided into sham operation,model and EA groups(n=34/group).The myocardial infarction model was established by permanent ligation of the anterior descending branch of the left coronary artery.Beginning from the 3rd day after ligation,EA(2 Hz/20 Hz)was applied to bilateral“Neiguan”(PC6)and“Ximen”(PC4)for 30 min,once a day for 28 days.The survival rate in 140 d was recorded and the left ventricular ejection fraction(EF)calculated by using echocardiography after the treatment.The left cardiac ventricular tissue was cut into sections to be stained with Masson’s trichrome,wheat germ agglutinin(WGA)orα-smooth muscle actin(α-SMA)immunohistochemistry method,followed by measuring the collagen area in the marginal region of myocardial infarction and calculating the collagen volume fraction(for assessing the severity of myocardial fibrosis),measuring the sectional area of cardiomyocytes(for assessing the degree of myocardial hypertrophy),and ob-serving the newborn blood vessels and calculating the ratio of neovascularization area(for assessing the state of angiogenesis).The expression of vascular endothelial growth factor(VEGF)and hypoxia-inducible factor(HIF)-1αprotein in the boundary area of myocardial infarction were detected by Western blot.Results After modeling,the survival rate,EF,and the thickness of the left cardiac ventricle were significantly decreased(P<0.01),whereas the percentage of collagen deposition area,sectional area of cardiomyocyte,percentage of angiogenesis area,and the expression levels of VEGF and HIF-1αproteins were significantly increased(P<0.01)in the model group relevant to the sham operation group.Compared with the model group,the survival rate,EF,the thickness of the left cardiac ventricle,the percentage of angiogenesis area,and the expression levels of VEGF and HIF-1αproteins were significantly increased(P<0.05,P<0.01),while the percentage of collagen deposition area and the sectional area of the cardiomyocyte were considerably decreased in the EA group(P<0.01,P<0.05).Conclusion EA of PC6 and PC4 can significantly improve the cardiac function and long-term survival rate in mice with myocardial infarction,which may be related to its functions in up-regulating the expression of HIF-1αand VEGF to promote angiogenesis and in inhibiting ventricular remodeling.