摘要
目的探究吡维氯铵对急性心肌梗死大鼠心肌纤维化和心脏功能的影响。方法分离并体外培养大鼠心肌成纤维细胞,设置正常环境和缺血缺氧环境,采用不用质量浓度(1,2,4,8,16,32和64μg·L^-1)的吡维氯铵作用于大鼠心肌成纤维细胞48 h,采用台盼蓝染色和血细胞计数板计数评价细胞存活率。结扎冠状动脉左前降支建立大鼠急性心肌梗死模型,将大鼠随机分为假手术组、心肌梗死组和吡维氯铵治疗组。急性心肌梗死术后14 d处死大鼠,采用心肌组织Masson染色评价心肌纤维化程度;采用α平滑肌肌动蛋白(α-SMA)染色观察心肌成纤维细胞的形成;测定羟脯氨酸含量评价心肌胶原含量;采用CD31染色评价毛细血管密度;采用超声心动图评价心脏功能。结果在缺血缺氧环境中,吡维氯铵能明显抑制心肌成纤维细胞的增殖,其IC 50值为11.7μg·L^-1;而吡维氯铵对正常条件下心肌成纤维细胞无抑制作用。与假手术组比较,心肌梗死组出现心肌梗死和心肌纤维化。与心肌梗死组大鼠比较,吡维氯铵治疗组心肌纤维化程度明显降低(P<0.01);α-SMA和心肌成纤维细胞数量明显减少(P<0.01);心肌胶原含量明显下降(P<0.05);CD31和毛细血管密度明显增加(P<0.01);治疗后大鼠左心室射血分数和左心室缩短分数明显改善(P<0.01),左心室舒张期末和收缩期末内径减小(P<0.05)。结论吡维氯铵能抑制急性心肌梗死后大鼠心肌纤维化,增加毛细血管新生,改善心功能。
Objective To investigate the effects of pyrvinium pamoate on myocardial fibrosis and cardiac function in rats after acute myocardial infarction.Methods Rat cardiac fibroblasts were isolated and cultured in vitro,and treated with different concentrations(1,2,4,8,16,32 and 64μg·L^-1)of pyrvinium pamoate under normal and ischemic/hypoxia environment.Trypan blue staining and blood count plate counting were used to detect the cell survival.Left anterior descending coronary artery ligation was performed to induce acute myocardial infarction.Rats were randomly assigned into sham-operated group,pyrvinium pamoate group and myocardial infarction group after surgery.Myocardial tissue Masson staining was used to observe the cardiac fibrosis.α-smooth muscle actin(α-SMA)immune-histochemical method was used to observe the formation of cardiac fibroblasts.Hydroxyproline content determination was used to detect the collagen content.CD31 staining was used to evaluate the capillary density.Echocardiagraphy was performed to evaluate the cardiac function.Results Pyrvinium pamoate could significantly inhibit the proliferation of myocardial fibroblasts under ischemic/hypoxia environment,its IC 50 value was 11.7μg·L^-1.But pyrvinium pamoate had no inhibitory effect under normal conditions.Compared with rats in the sham-operated group,myocardial infarction group showed myocardial infarction and myocardial fibrosis.Compared with rats in the myocardial infarction group,pyrvinium pamoate treatment could reduce the myocardial fibrosis(P<0.01),the number ofα-SMA and myocardial fibroblasts decreased significantly(P<0.01),the content of myocardial collagen decreased significantly(P<0.05),CD31 and capillary density increased significantly(P<0.01),the left ventricular systolic ejection fraction and left ventricular fractional shortening were improved significantly(P<0.01),the left ventricular end-diastolic diameter and left ventricular end-systolic diameter were decreased significantly(P<0.05).Conclusion Pyrvemonium chloride can inhibit my
作者
牛轶
李魏林
NIU Yi;LI Weilin(Xiangyang Central Hospital,Affiliated Hospital of Hubei University of Arts and Science,Xiangyang 441003,China)
出处
《西北药学杂志》
CAS
2019年第6期779-783,共5页
Northwest Pharmaceutical Journal
关键词
吡维氯铵
急性心肌梗死
心肌纤维化
心功能
pyrvinium pamoate
acute myocardial infarction
myocardial fibrosis
cardiac function
