冠心丹参滴丸联合诱导多能干细胞来源的心肌细胞移植对大鼠心肌梗死的影响  

Effects of Guanxin Danshen Dropping Pills Combined with Induced Pluripotent Stem Cell Derived Cardiomyocyte Transplantation in Rats with Myocardial Infarction

作　　者：蔡昊[1] 罗志荣[1] 韩小晶[1] 牟芳芳[1] 邵水金[1] 国海东[1,2] CAI Hao;LUO Zhirong;HAN Xiaojing;MOU Fangfang;SHAO Shuijin;GUO Haidong(School of Basic Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Academy of Integrative Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学基础医学院,上海201203 [2]上海中医药大学中西医结合研究院,上海201203

出　　处：《中国中医药信息杂志》2022年第11期60-66,共7页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金(82174120、81673729)。

摘　　要：目的观察冠心丹参滴丸联合人诱导多能干细胞(iPSC)来源的心肌细胞移植对心肌梗死(MI)大鼠心功能的影响,探讨其可能的作用机制。方法体外培养iPSC并诱导其分化成心肌细胞。将50只大鼠随机分为假手术组、模型组、细胞移植组、冠心丹参滴丸组和冠心丹参滴丸+细胞移植组(联合组),每组10只,采用结扎左冠状动脉前降支建立MI大鼠模型。相应方法干预4周后,采用超声心动图检测大鼠心功能,Masson染色检测大鼠心肌梗死面积和胶原纤维沉积,ELISA检测梗死心肌组织和血清基质细胞衍生因子-1(SDF-1)、干细胞因子(SCF)、血管内皮生长因子(VEGF)含量。结果与假手术组比较,模型组大鼠左室射血分数(EF)、左室短轴缩短分数(FS)明显降低(P<0.01),左室舒张末期内径(LVDd)、左室收缩末期内径(LVDs)、左室舒张末期容积(LVEDV)、左室收缩末期容积(LVESV)明显升高(P<0.01),心肌梗死面积和胶原纤维含量明显增加(P<0.01),梗死心肌组织和血清SDF-1、SCF、VEGF差异无统计学意义;与模型组比较,细胞移植组和联合组大鼠EF、FS明显升高(P<0.01),LVDs、LVESV明显降低(P<0.01),心肌组织梗死面积和胶原纤维含量明显减少(P<0.01),细胞移植组、冠心丹参滴丸组和联合组大鼠梗死心肌组织SDF-1、SCF、VEGF含量明显增加(P<0.01),联合组大鼠血清SDF-1、VEGF含量明显增加(P<0.01),联合组总体效果优于细胞移植组和冠心丹参滴丸组。结论冠心丹参滴丸联合iPSC来源的心肌细胞移植可以提高MI模型大鼠心功能,减少梗死面积,其机制可能与促进旁分泌有关。Objective To observe the effect of Guanxin Danshen Dropping Pills combined with human induced pluripotent stem cell(iPSC)derived cardiomyocyte transplantation on cardiac function in myocardial infarction(MI)rats and explore its possible mechanism.Methods The iPSC were cultured in vitro and induced to differentiate into cardiomyocytes.Totally 50 rats were divided into sham-operation group,model group,iPSC derived cardiomyocyte transplantation group(iPSC group),Guanxin Danshen Dropping Pills group(GXDS group)and Guanxin Danshen Dropping Pills combined with iPSC derived cardiomyocyte transplantation group(combination group),with 10 rats in each group.The MI model was established by ligating the left anterior descending coronary artery.After 4 weeks of treatment,the changes of cardiac function in each group were detected by echocardiography,the collagen deposition in the infarct area and infarct size were detected by Masson staining,and the contents of SDF-1,SCF and VEGF in infarcted myocardium tissue and serum were detected by ELISA.Results Compared with the sham operation group,the left ventricular ejection fraction(EF)and left ventricular shortening fraction(FS)of rats in the model group significantly decreased(P<0.01),the left ventricular end diastolic diameter(LVDd),left ventricular end systolic diameter(LVDs),left ventricular end diastolic volume(LVEDV),and left ventricular end systolic volume(LVESV)significantly increased(P<0.01),the myocardial infarction area and collagen fiber content significantly increased(P<0.01),there was no stastical significance in SDF-1,SCF and VEGF content.Compared with the model group,the EF and FS in iPSC group and combination group significantly increased(P<0.01),the LVDs and LVESV significantly decreased(P<0.05,P<0.01),the myocardial infarction area and collagen fiber content significantly decreased(P<0.01),the contents of SDF-1,SCF and VEGF in infarcted myocardium tissue of iPSC group,GXDS group and combination group significantly increased(P<0.01),and the contents of serum SDF-

关 键 词：冠心丹参滴丸 诱导多能干细胞 移植 心功能 旁分泌 

分 类 号：R285.5[医药卫生—中药学] Q28[医药卫生—中医学]