活血安心方减轻急性心肌梗死大鼠心肌缺血损伤的实验研究

Experimental Study on Attenuating Ischemic Injury of Acute Myocardial Infarction Rats by Huoxue Anxin Recipe

目的观察活血安心方对急性心肌梗死(AMI)大鼠心肌缺血损伤的防治作用及其机理。方法对Wistar大鼠行冠状动脉左前降支结扎制作AMI模型,以长效异乐定为阳性对照药,活血安心方依据现代药学制剂方法提取各有效组分进行配伍,给药时间为造模当天至造模后21d,观察心功能、心脏形态改变及toll样受体4-核因子κB-肿瘤坏死因子α(TLR4-NFκB-TNFα)通路mRNA和蛋白水平的变化。结果与假手术组比较,模型组心脏射血分数(EF)和左心室缩短分数(FS)显著下降(P<0.01),左心室舒张末期内径(LVIDd)和左心室收缩末期内径(LVIDs)显著增大(P<0.01),TLR4-NFκB-TNFα通路mRNA和蛋白表达水平显著增加(P<0.01),左心室前壁梗死明显并伴有严重的炎细胞浸润和胶原纤维沉积;与模型组比较,阳性药组及活血安心方高、低剂量组EF和FS显著升高,LVIDd和LVIDs显著减小(P<0.05,P<0.01),左心室前壁梗死面积明显缩小,炎细胞浸润和胶原纤维沉积也明显减轻。活血安心方高、低剂量组还显著降低TLR4-NFκB-TNFα通路mRNA和蛋白表达水平(P<0.05,P<0.01),而阳性药组对该通路无抑制作用。结论活血安心方能显著改善AMI大鼠心肌缺血损伤导致的心脏形态结构和功能异常,该作用与其抑制TLR4-NFκB-TNFα通路激活有关。

Objective To study the protection effects and the mechanisms of Huoxue Anxin Recipe （HAR） on acute myocardial infarction （AMI） rats. Methods The AMI Wistar rat model was prepared by ligating the left anterior descending coronary artery. By taking elanfan long as the positive control drug, HAR was extrac- ted from Chinese herbs by modern pharmacological methods and composed according to theories of Chinese medicine （CM）. The medication time started from the day of modeling to the 21 st day of the modeling. The heart function, the morphological changes of the heart, changes in the mRNA and protein levels of toll like receptor 4 nuclear factor kappa B tumor necrosis factor c~ （TLR4-NFKB-TNFc~） pathway were observed. Results Compared with the sham-operation group, the ejection fraction （EF） and left ventdcular fractional shortening （FS） signifi- cantly decreased （P 〈0.01 ）, the left ventricular internal dimension end-diastolic （LVIDd） and left ventricular in- ternal dimension end-systolic （LVIDs） significantly increased （ P 〈0.01 ）, the mRNA and protein levels of TLR4- NFKB-TNFa channel significantly increased in the model group （P 〈0.01 ）. The infarction in the front wall of the left ventricle was obviously seen, accompanied with severe inflammatory cell infiltration and collagen deposition in model group. Compared with the model group, the EF and FS significantly increased, LVlDd and LVIDs signifi- cantly decreased in the positive control group, the high and low dose HAR groups （P〈0.05, P〈0.01 ）. The in- fracted area of the front wall of the left ventricle was obviously contracted. The inflammatory cell infiltration and collagen deposition were obviously alleviated. In the high and low dose HAR groups, the mRNA and protein ex- pression levels of TLR4-NFKB-TNFa significantly decreased （ P 〈0.05, P 〈0.01 ）, but no inhibition was found inthe positive control group. Conclusions HAR could significantly improve the morphological structures and func- tional abnormality induced by myocardial ischemia in AMI rats. Its effects was correlated with inhibiting TLR4- NFKB-TNFa pathway.