心悦胶囊对大鼠心梗后缺血心肌骨桥蛋白和腱糖蛋白表达的影响

Effect of Xinyue capsule on protein expression of ischemic myocardial osteopontin and tenascin-C in rats after myocardial infarction

目的观察心悦胶囊(xinyue capsule,XYC)对大鼠急性心肌梗死(acute myocardial infarction,AMI)后早期心室重构(ventricular remodeling,VR)心功能及缺血心肌骨桥蛋白(osteopontin,OPN)和腱糖蛋白(tenascin-C,TN-C)表达的影响,从细胞外基质(extracellular matrix,ECM)代谢途径探讨心悦胶囊可能的作用机制。方法结扎Wistar大鼠冠状动脉前降支制备AMI模型,将60只造模成功的大鼠随机分为4组,每组15只,分别为假手术组(冠状动脉前降支仅穿线不结扎)、模型组、缬沙坦组(灌胃缬沙坦7.2 mg·kg·d-1)、心悦胶囊组(灌胃心悦胶囊162 mg·kg-1·d-1)。各组药物配成相同容量,d 2开始灌胃给药,连续4周,假手术组和模型组灌胃等剂量蒸馏水。4周后,超声心动图检查大鼠心脏结构及心功能变化,HE染色观察心肌组织病理变化,免疫组织化学染色法半定量检测缺血心肌OPN、TN-C的表达水平。放射性免疫法检测心肌组织血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)、醛固酮(aldosterone,ALD)、转化生长因子β1(tissue growth factor-β1,TGF-β1)含量。结果和模型组相比,心悦胶囊组心脏左室舒张末内径明显降低,左室射血分数明显提高(P<0.05),室间隔收缩和舒张末期厚度明显增加(P<0.05)。心悦胶囊组缺血心肌组织OPN表达明显降低(P<0.01)、TN-C表达亦明显降低(P<0.05)。心悦胶囊组心肌组织AngⅡ、ALD和TGF-β1含量明显降低(P<0.01)。结论心悦胶囊可改善大鼠AMI后的早期心室重构和心功能,机制涉及其有效成分西洋参茎叶总皂苷通过减少神经内分泌因子生成,减轻炎症反应,降低OPN、TN-C表达进而调节细胞外基质代谢。

Aim To investigate the effect of xinyue capsule （XYC） on protein expression of ischemic myo- cardial osteopontin （ OPN ）, tenascin-C （ TN-C ） and heart function during prophase ventricular remodeling （VR） after acute myocardial infarction （AMI） in rats. Meanwhile, explore the possible mechanism on extra- cellular matrix （ ECM ） metabolism. Methods The AMI model was established by ligating the left anterior descending coronary artery of rats to induce myocardial infarction. 60 Wistar rats with model establishment were randomly divided into 4 groups, I5 rats in each group. They were sham group （the suture was penetra- ted around the left anterior descending coronary artery, but not tied） , model group, valsartan group of which valsartan was given 7.2 mg· kg^-1 · d^- 1 , XYC group of which XYC was given 162 mg · kg ^-1· d^-1. All of the medicine was given by garage from the second day after model establishment. Both sham and model group were administered with equivalent distilled water. Aftercontinuous intragastric administration of 4 weeks, ul- trasonic cardiography was used to examine the morpho- logic change and heart function. HE staining was used to observe the myocardial pathological change. The protein expression of OPN and TN-C in myocardial tis- sue was tested semiquantitatively by immunohistochem- ical method. Myoeardium contents of angiotensin Ⅱ （ Ang Ⅱ ）, aldosterone （ ALD ） and tissue growth fac- tor-β1 （TGF-β1） were tested by radioimmunoassay method. Results Compared with model group： 1 left ventricular end-systole dimension （ LVED ） reduced significantly and left ventrieular ejection fraction （LVEF） increased significantly in PQS group （P 〈 0.05）; 2 both interventricular septum end-diastole thickness （IVSTd） and interventrieular septum end- systole thickness （IVSTs） increased significantly in XYC group （ P 〈 0.05 ） ;3 isehemie myoeardium pro- tein expression of OPN decreased significantly in XYC group （ P 〈 0. 0 1 ） and TN-C decreased significantly inXYC group （ P 〈 0.05 ） ; （4） myocardial tissue contents of Ang II , ALD and TGF-Ⅱ1 decreased significantly in XYC group（P〈0.05, P〈0.01）. Conclusion XYC can improve the heart function by attenuating the pro- phase VR of rats after AMI. The possible mechanism of the improvement is that panax quinquefolius saponin （PQS） effective constituent of XYC can regulate ECMmetabolism by inhibiting neuroendocrine factors pro- duction, alleviating inflammation reaction and reducing ischemic myocardial protein expression of OPN and TN-C.