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

作　　者：刘依 常丽萍 尹玉洁 韩宁馨 贾振华[1,2,3,4] LIU Yi;CHANG Liping;YIN Yujie;HAN Ningxin;JIA Zhenhua(Graduate School of Hebei Medical University,Shijiazhuang 050017,China;National Key Laboratory of Collateral Disease Research and Innovative Traditional Chinese Medicine(TCM),Shijiazhuang 050035,China;Key Research Office of State Administration of TCM Cerebrovascular Diseases,Shijiazhuang 050035,China;Hebei Academy of Integrated Traditional Chinese and Western Medicine,Shijiazhuang 050035,China)

机构地区：[1]河北医科大学研究生学院,石家庄050017 [2]络病研究与创新中药国家重点实验室,石家庄050035 [3]国家中医药管理局重点研究室(心脑血管络病),石家庄050035 [4]河北省中西医结合医药研究院,石家庄050035

出　　处：《中国实验方剂学杂志》2024年第21期86-94,共9页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金重点项目(2023YFC3504303)。

摘　　要：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

关 键 词：人参皂苷Rg_(1) 水蛭素 急性心肌梗死 心肌纤维化 内皮间质转分化 

分 类 号：R2-0[医药卫生—中医学] R22R285.5R289R33