内皮细胞特异性分子-1预处理干细胞用于心肌梗死治疗的实验研究

Experimental research on treatment of myocardial infarction by stem cells pretreated with endothelial cell-specific molecule-1

目的:探讨内皮细胞特异性分子-1(endothelial cell-specific molecule 1,ESM-1)预处理的大鼠骨髓间充质干细胞(bone marrow-derived mesenchymal stem cells,BM-MSCs)植入心肌梗死(MI)大鼠后,是否能增加干细胞的存活,改善MI大鼠的心功能。方法:将用5-溴脱氧尿嘧啶核苷(Brd U)标记的BM-MSCs与ESM-1孵育预处理后,以注射器自心外膜注入SD大鼠梗死心肌周围组织。将30只SD大鼠随机分为3组,即空白组、对照组及预处理组,每组10只大鼠(n=10)。于MI后4周、干细胞移植后4周分别检测各组的超声参数:左室射血分数(LVEF)、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、室间隔厚度(IVST)和左室后壁厚度(LVPWT);用ELISA法定量检测血清脑钠尿肽(BNP)的分泌以及移植细胞的存活情况。结果:干细胞移植后4周,预处理组大鼠心脏超声检测提示LVESD、LVEDD缩小、LVEF提高,BNP含量降低,与对照组比较差异具有统计学意义(P<0.01)。干细胞移植后4周,预处理组梗死周围心肌组织Brd U+的细胞数明显增多,与对照组比较差异具有统计学意义(P<0.01)。结论:将ESM-1与BM-MSCs共孵育可活化BM-MSCs,促进其增殖、分化,改善心功能。

AIM： To explore whether the transplantation of rat bone marrow mesenchymal stem cells （BM-MSCs） pretreated by endothelial cell specific molecule-1 （ESM-1） into myocardial infarction （MI） rats can increase the stem cell survival and improve the heart function of MI rats. METHODS： ESM-1-pretreated and BrdU-marked MSCs were injected by syringe from epicardial tissue surrounding the infarcted myocardium in Sprague Dawley （SD） rats. Thirty SD rats were randomly divided into three groups： blank group, control group and preconditioning group, with ten rats in each group. Four weeks after myocardial infarction and 4 weeks after cell transplantation, ultrasonic parameters were, respectively, detected in each group. The detected parameters included left ventricular ejection fraction （LVEF） , left ventricular end diastolic diameter （LVEDD）, left ventricular end systolic diameter （LVESD）, interventricular septal thickness （IVST） and left ventricular posterior wall thickness （LVPWT）. ELISA method was used for quantitative detection of serum brain natriuretic peptide （BNP） secretion and the survival of the transplanted cells. RESULTS ： Four weeks after cell transplantation, LVESD and LVEDD were reduced, LVEF increased and the content of BNP in plasma decreased in preconditioning group, with statistical significance between preconditioning group and control group （ P 〈 0. 01 ）. The number of BrdU ＋ cells around infarcted myocardium in preconditioning group significantly increased compared with that in control group （P 〈0.01）. CONCLUSION： ESM-1 incubated with MSCs can activate MSCs and promote their proliferation and differentiation, thus improving heart function.