冠心宁对急性心肌梗死大鼠心肌保护及促再生的作用及机制

Effect and mechanism of Guanxinning on myocardial protection and regeneration in rats with acute myocardial infarction

目的探讨冠心宁对急性心肌梗死(AMI)大鼠心肌保护及促再生的作用,并分析其中作用机制。方法通过结扎SD大鼠左前降支冠脉建立大鼠AMI模型,将建模成功的72只大鼠随机分为六组,假手术组、模型组、阿托伐他汀组、冠心宁高剂量(600 mg/kg)组、中剂量(300 mg/kg)组和低剂量(150 mg/kg)组,各12只。灌胃14 d后,观察各组大鼠心肌梗死周边结构改变;比较各组大鼠心肌梗死面积、心功能指标及血管新生情况。结果苏木精-伊红(HE)染色显示,冠心宁组心肌病理损伤相对较轻;Masson染色显示,模型组、阿托伐他汀组和冠心宁组心肌组织中胶原纤维含量显著增加,纤维瘢痕形成,其中模型组较为显著。模型组心肌梗死面积明显高于假手术组(t=42.35,P<0.05);与模型组比较,阿托伐他汀组、冠心宁组心肌梗死面积明显缩小(F=36.71,P<0.05),且冠心宁中高剂量组心肌梗死面积缩小更为显著(P<0.05)。给药14 d后,阿托伐他汀组及冠心宁组(低、中、高剂量)左心室射血分数(LVEF)、左室缩短率(LVFS)值高于模型组(t分别=3.91、4.42;3.88、4.55;13.13、8.06;13.35、8.52,P均<0.05),且冠心宁中、高剂量组LVEF、LVFS值高于阿托伐他汀组、冠心宁低剂量组(t分别=9.46、3.91;9.77、4.45;9.12、3.65;9.44、4.18,P均<0.05)。与假手术组比较,模型组、阿托伐他汀组及冠心宁组血管内皮细胞生长因子(VEGF)、碱性成纤维生长因子(bFGF)蛋白相对表达量明显升高(t分别=3.33、6.77;8.88、10.81;9.19、11.60;13.76、10.85;12.11、10.41,P均<0.05);与模型组比较,阿托伐他汀组、冠心宁组(低、中、高剂量)VEGF、bFGF蛋白相对表达量明显升高(t分别=4.22、4.00;4.62、4.37;10.90、6.42;9.80、6.29,P均<0.05),且冠心宁中、高剂量组VEGF、bFGF蛋白相对表达量较阿托伐他汀组、冠心宁低剂量组更高(t分别=8.30、3.43;7.47、3.46;7.91、3.29;7.14、3.33,P均<0.05)。结论冠心宁可改善AMI大鼠心肌超微结构,起到心肌保护及再生的作用,其具体机制与改善微循环、促血管新生、降低氧化应激损伤有关,其中中、高剂量冠心宁对AMI大鼠心肌保护及再生作用效果更佳。

Objective To investigate the effect of Guanxinning on myocardial protection and regeneration in rats with acute myocardial infarction(AMI),and analyze its mechanism.Methods Rat AMI model was established by ligating the left anterior descending coronary artery of SD rats.Seventy-two rats were randomly divided into 6 groups:sham operation group,model group,atorvastatin group,Guanxinning high-dose(600 mg/kg)group,medium-dose(300 mg/kg)group and low-dose(150 mg/kg)group,12 rats in each.After 14 days of intragastric administration,the changes of the structure around the infarction were observed.The myocardial infarction area,cardiac function index and angiogenesis of rats in each group were compared.Results HE staining showed that myocardial pathological damage in Guanxinning group was relatively mild.Masson staining showed that the content of collagen fibers in myocardial tissue of model group,atorvastatin group and Guanxinning group increased significantly,and the formation of fibrous scar was more significant in model group.The myocardial infarction area of model group was significantly higher than that of sham operation group(t=42.35,P<0.05).Compared with the model group,the myocardial infarction area of atorvastatin group and Guanxinning group decreased significantly(F=36.71,P<0.05),and the myocardial infarction area of Guanxinning medium and high dose group decreased more significantly.After 14 days of administration,the left ventricular ejection fraction(LVEF)and left ventricular shortening rate(LVFS)in atorvastatin group and Guanxinning group were higher than those of model group(t=3.91,4.42,3.88,4.55,13.13,8.06,13.35,8.52,P<0.05),and the LVEF and LVFS values of Guanxinning medium and high dose group were relatively higher than those of the atorvastatin group and Guanxinning low-dose group(t=9.46,3.91,9.77,4.45,9.12,3.65,9.44,4.18,P<0.05).Compared with the sham operation group,the relative expression of vascular endothelial growth factor(VEGF)and basic fibroblast growth factor(bFGF)protein in the model group,atorvastatin group and Guanxinning group were significantly higher(t=3.33,6.77,8.88,10.81,9.19,11.60,13.76,10.85,12.11,10.41,P<0.05).Compared with the model group,the relative expression of VEGF and bFGF protein in atorvastatin group and Guanxinning group was significantly higher(t=4.22,4.00,4.62,4.37,10.90,6.42,9.80,6.29,P<0.05),and the relative expressions of VEGF and bFGF protein in Guanxinning medium-and high-dose groups was relatively higher than those of the atorvastatin group and Guanxinning low-dose group(t=8.30,3.43,7.47,3.46,7.91,3.29,7.14,3.33,P<0.05).Conclusion Guanxinning can improve the myocardial ultrastructure of AMI rats,and play a role in myocardial protection and regeneration.The specific mechanism is related to improving microcirculation,promoting angiogenesis,and reducing oxidative stress damage.The effect of medium-and high-dose of Guanxinning on myocardial protection and regeneration of AMI rats is better.