参附益心颗粒对心肌梗死后心力衰竭大鼠心肌纤维化的影响  

Effects of Shenfu Yixin Granules (参附益心颗粒) on Myocardial Fibrosis in Rats with Post-infarction Heart Failure

作　　者：程彦玲 谢世阳 王小晓 崔琳 刘素晓 李彬 朱明军 CHENG Yanling;XIE Shiyang;WANG Xiaoxiao;CUI Lin;LIU Suxiao;LI Bin;ZHU Mingjun(The First Affiliated Hospital,Henan University of Chinese Medicine,Zhengzhou 450000,China)

机构地区：[1]河南中医药大学第一附属医院

出　　处：《中医杂志》2020年第1期68-73,共6页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(81603466,81503419,81703897,81373853);河南省创新型科技团队(C20130050)

摘　　要：目的观察参附益心颗粒对心肌梗死后心力衰竭大鼠心肌纤维化的影响及可能作用机制。方法采用结扎大鼠左冠状动脉前降支的方法制备心肌梗死模型,将造模成功的32只SD大鼠随机分为模型组、参附常用量组、参附高剂量组、氯沙坦组,另设只穿线不结扎的假手术组,均每组8只。参附常用量组和参附高剂量组分别给予参附益心颗粒1.76、8.8g/(kg•d)灌胃,氯沙坦组给予氯沙坦片10mg/(kg•d)灌胃,假手术组和模型组给予蒸馅水1 ml/(100g-d)灌胃。4周后超声心动图评价各组大鼠心脏功能,并计算左室重量指数(LVWI);Masson染色法及轻脯氨酸测定法测定心肌组织胶原蛋白分布及含量;Western blot法确定心肌组织转化生长因子pi(TGF-01)、Smad 2、Smad 3的蛋白表达量;RT-PCR法检测微小RNA-21(miR-21)和转化生长因子BID型受体(TGF-BRID)mRNA的表达水平。结果与模型组比较,参附常用量组、参附高剂量组、氯沙坦组左室收缩末内径(LVESD)减小、左室射血分数(LVEF)和左室短轴缩短率(LVFS)升高,LVW1和胶原蛋白含量下降,同时心肌组织TGF-(31、Smad 3蛋白表达量和miR-21的mRNA表达水平降低,TGF-pRin mRNA表达水平升高(P<0.05或P<0.01);与参附常用量组比较,参附高剂量组LVESD减小、LVEF、LVFS和心肌组织TGF-pRin mRNA表达升高(P<0.05或P<0.01)。结论参附益心颗粒可改善心力衰竭大鼠心肌纤维化,抑制心室重构,提高心脏功能,其作用机制可能与调控miR-21从而抑制TGF-01/Smads信号通路的过度激活有关。Objective To observe the effects of Shenfu Yixin Granules(参附益心颗粒)(SFYX)on the myocardial fibrosis of rats with post-infarction heart failure(HF)and to explore the possible mechanism.Methods A model of myocardial infarction was prepared by ligating the left anterior descending coronary artery of rats.The 32 successfully modeled rats were randomly divided into a model group,a normal dose SFYX group,a high dose SFYX group and a losartan group.A sham operation group that was only threaded but not ligated was set,with 8 rats in each group.The normal dose SFYXgroup and the high dose SFYX group were given the corresponding drugs by gavage at 1.76 and 8.8 g/(kg•d),and the losartan group was given losartan tablets at 10 mg/(kg•cl)by gavage.The sham operation group and the model group were given by gavage with distilled water at 1 ml/(100 g・d).Cardiac function was evaluated by echocardiography after 4 weeks,and left ventricular weight index(LVWI)was calculated.The distribution and content of myocardial collagen were determined by Masson staining and hydroxyproline assay.Myocardial transformation growth factor[Bl(TGF-pl),Smad 2 and Smad 3 protein expression levels were determined by wstern blot;RT-PCR method was used to detect miR-21 and transforming growth factor 0 type HI receptor(TGF-pR ID)mRNA expression levels.Results Compared with the model group,left ventricular end systolic diameter(LVESD)was decreased,left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS)were significantly increased,and LVMI and collagen contents were decreased,and also TGF-pl,Smad3 protein ex・pression and miR-21 gene expression levels were depressed,while TGF-0R皿was increased in the normal dose of SFYX group,the high dose of SFYX group,and the losartan group(P<0.05 or P<0.01).Conclusion SFYX can attenuate myocardial fibrosis,inhibit ventricular remodeling and improve cardiac function in rats with HF,whose mechanism might be related with regulating miR-21 so as to inhibit the excessive activatio

关 键 词：心力衰竭 心肌纤维化 参附益心颗粒 TGF-Rl/Smads信号通路 微小RNA-21 

分 类 号：R285.5[医药卫生—中药学]