人参皂苷Rg_(1)联合水蛭素对急性心肌梗死后心肌纤维化小鼠的作用及机制

Effect and Mechanism of Ginsenoside Rg_(1)Combined with Hirudin in Treating Myocardial Fibrosis in Mice After Acute Myocardial Infarction

目的:探讨人参皂苷Rg(1 G-Rg_(1))联合水蛭素(Hirudin)对急性心肌梗死(AMI)心肌纤维化小鼠的作用及可能机制。方法:75只C57BL/6N小鼠随机分成假手术组(Sham组)、模型组(Model组)、G-Rg(120 mg·kg^(-1))组、Hirudin(20 mg·kg^(-1))组、G-Rg(120 mg·kg^(-1))+Hirudin(20 mg·kg^(-1))组。结扎小鼠左冠状动脉前降支建立AMI模型,持续灌胃4周。通过结扎前后小鼠心电图变化判断模型成功与否、检测每组心脏指数、超声心动图、心肌纤维化、Ⅰ型胶原蛋白α1链(COL1A1)、血小板-内皮细胞黏附分子(PECAM-1/CD31)、α-平滑肌肌动蛋白(α-SMA)内皮间质转分化(EndMT)相关指标、细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子-1(VCAM-1)的变化。结果:结扎左冠状动脉前降支后,R波与T波之间融合为高大的帐篷状波,出现“损伤型”ST段改变,提示模型制备成功;与Sham组比较,Model组毛发暗淡干枯且行动迟缓;心脏指数显著升高(P<0.01);左室射血分数(EF)和左室缩短分数(FS)水平显著下降(P<0.01),左室舒张末期内径(LVEDd)和左室收缩末期内径(LVESd)水平显著升高(P<0.01);心肌纤维排列无序,大量胶原纤维显著增生(P<0.01),COL1A1蛋白表达显著增加(P<0.01);ICAM-1、VCAM-1蛋白水平显著升高(P<0.01);CD31表达下降,α-SMA表达显著上调(P<0.01)。与模型组比较,各治疗组上述指标均得到不同程度改善(P<0.05,P<0.01),且联合组效果更佳(P<0.01)。结论:G-Rg_(1)联合水蛭素具有改善AMI后心肌纤维化的作用,其机制可能与抑制心脏组织黏附分子蛋白表达,减少炎性细胞黏附,减轻心脏炎症、抑制心脏EndMT有关。

Objective:To investigate the effect and mechanism of ginsenoside Rg_(1)(G-Rg_(1))combined with hirudin in treating myocardial fibrosis in the mouse model of acute myocardial infarction(AMI).Method:Seventy-five C57BL/6N mice were randomized into sham,model,G-Rg_(1)(20 mg·kg^(-1)),hirudin(20 mg·kg^(-1)),and G-Rg_(1)(20 mg·kg^(-1))+hirudin(20 mg·kg^(-1))groups.The mouse model of AMI was established by ligation of the anterior descending branch of the left coronary artery and continued gavage for 4 weeks.The success of the modeling was judged by ECG changes of mice before and after ligation.The heart weight index,echocardiography,myocardial fibrosis,typeⅠcollagenα1(COL1A1),platelet-endothelial cell adhesion molecule-1(PECAM-1/CD31),α-smooth muscle actin(α-SMA),intercellular adhesion molecule-1(ICAM-1),and vascular cell adhesion molecule-1(VCAM-1)were measured before and after treatment.Result:After ligation of the anterior descending branch of the left coronary artery,the R wave and T wave merged into a tall tented wave,and the ST segment presented a"damaged"change,indicating that the model was successfully prepared.Compared with the sham group,the model group showed dull and dry hair,slow movement,increased heart weight index(P<0.01),decreased left ventricular ejection fraction(EF)and left ventricular shortening fraction(FS)(P<0.01),increased left ventricular end-diastolic diameter(LVEDd)and left ventricular end-systolic diameter(LVESd)(P<0.01),disarranged myocardial fibers,collagen fiber hyperplasia(P<0.01),increased expression of COL1A1(P<0.01),upregulated protein levels of ICAM-1 and VCAM-1(P<0.01),downregulated CD31 expression,and upregulatedα-SMA expression(P<0.01).Compared with the model group,the treatment groups recovered the above indexes in different degrees(P<0.05,P<0.01),and the combined group had better effect(P<0.05).Conclusion:G-Rg_(1)combined with hirudin can ameliorate myocardial fibrosis after AMI by inhibiting the expression of adhesion molecular protein in the heart tissue,reducing the adhesion of inflammatory cells,alleviating cardiac inflammation,and inhibiting cardiac endothelialto-mesenchymal transition.