17β-雌二醇预处理的骨髓源性内皮祖细胞治疗急性心肌梗死的实验研究

Transplantation of bone marrow-derived endothelial progenitor cells preconditioned with ex vivo 17β-estradiol enhances healing efficacy after acute myocardial infarction

目的 探讨17β-雌二醇预处理的骨髓源性内皮祖细胞（BM-EPC）对小鼠急性心肌梗死的治疗作用.方法 培养和鉴定卵巢切除小鼠BM-EPC.建立卵巢切除小鼠急性心肌梗死模型,分为17β-雌二醇＋BM-EPC组、BM-EPC组和对照组,每组6只.心肌梗死后3 d,分别经尾静脉注射17β-雌二醇处理或未处理的BM-EPC,对照组注射等体积的生理盐水.细胞输注后25 d,分别用心脏超声检测心功能,免疫组织化学染色检测新生血管密度,Masson染色检测左心室纤维化程度等指标.结果 17β-雌二醇＋BM-EPC组心功能、新生血管密度和心室纤维化程度等指标明显优于对照组[左心室收缩末内径：（3.09±0.05）mm比（3.27±0.10）mm,P〈0.05;左心室舒张末内径：（4.18 ±0.07）mm比（4.31±0.05）mm,P〈0.05;左心室缩短分数：33.0%±3.8%比26.0%±3.2%,P〈0.05;新生血管密度：（1428±214）个/mm2比（1070±168）个/mm2,P〈0.05;左心室纤维化面积百分比：38.8%±4.9%比49.0%±4.6%,P〈0.05],而BM-EPC组与对照组差异无统计学意义（P〉0.05）.结论 17β-雌二醇预处理能促进体内BM-EPC介导的新生血管生成、减轻心室纤维化,从而改善心功能.

Objective To investigate the therapeutic efficacy of intravenous implanted bone marrowderived endothelial progenitor cells（BM-EPC）preconditioned with 17β-estradiol in ovariectomized mice model of acute myocardial infarction（AMI）.Methods BM-EPC were cultured and identified from ovariectomized BAI-B/C mice tibia and femur.The ovariectomized BALB/C mice models of acute myocardial infarction（AMI）were established,and randomly divided into 17β-estradiol＋BM-EPC group（n=6）,BM-EPC group（n=6）and control group（n=6）.Three days after AMI,BM-EPC pretreated with or without 17β-estradiol was infused via tail vein.The equal volume of saline was infused in control group.Twenty-five days after infusion,left ventricular（LV）function and dimensions,capillary density and ratio of fibrosis area to LV area were measured.Results LV function and dimensions,capillary density and LV fibrosis were significantly improved in 17β-estradiol＋BM-EPC group than in control group[（LVDs：（3.09±0.05）mm vs.（3.27±0.10）mm,P〈0.05;LVDd：（4.18 ±0.07）mm vs.（4.31±0.05）mm,P〈0.05;FS：（33.0 ±3.8）%vs.（26.0 ±3.2）%,P〈0.05;capillary density：（1428 ±214）/mm2 vs.（1070 ±168）/mm2,P〈0.05;ratio of fibrosis：（38.8 ±4.9）%vs.（49.0±4.6）%,P〈0.05].However,Above mentioned parameters were similar between BM-EPC group and control group（P〉0.05）.Condusions BM-EPC preconditioned with 17β-estradiol can enhance capillary density,decrease LV fibrosis and improve cardiac function in this mice model of AMI.