骨髓间充质干细胞移植与肝细胞生长因子转导对猪心肌梗死后心力衰竭治疗作用的比较Comparative study between bone marrow cell transplantation and Ad5-HGF transfer via noninfarct-relative artery on neovascularization and heart function after myocardial infarction in swine
王连生,王伟,杨志健,马东超,徐顺霖,张郁青,周芳,陈波,曹克将,马文珠
摘要(Abstract)：
目的研究经猪非梗死相关动脉分别移植骨髓间充质干细胞(bone marrow-derivedmes-enchymal stem cells,BM-MSCs)或腺病毒介导肝细胞生长因子(adenovirus5-hepatocyte growth factor,Ad5-HGF)对心肌梗死的治疗作用。方法苏中幼猪18只,分为3组:BM-MSCs组、Ad5-HGF组与对照组。3组均经开胸结扎冠状动脉前降支制作心肌梗死模型。BM-MSCs组结扎后2周抽取骨髓分离培养BM-MSCs,并在结扎后4周经非梗死相关动脉注入梗死心脏(剂量5×106/mL)。Ad5-HGF组于结扎后4周经非梗死相关动脉注入Ad5-HGF4×109pfu。对照组则注入同样量的细胞培养液(IMDM)。三组均在结扎后4周和7周行门控心肌显像评价心肌灌注及心功能,并在7周处死动物,取心脏标本,行免疫组化检查。结果(1)免疫组化结果:在两治疗组与对照组梗死周边区均可见新生血管,BM-MSCs组和Ad5-HGF组的新生血管密度(毛细血管密度分别为102·4±8·6/mm2和105·3±7·7/mm2,功能血管密度分别为52·1±4·1/mm2和66·0±3·3/mm2)均高于对照组(毛细血管密度55·5±4·7/mm2,功能血管密度16·4±3·5/mm2),P均<0·01。(2)门控心肌显像:治疗后4周两治疗组及对照组间左室射血分数(LVEF)值差异均无统计学意义;治疗后7周BM-MSCs组和Ad5-HGF组LVEF值(45·0±2·7和43·9±4·3)明显优于对照组(30·4±2·8),差异均有统计学意义(P均<0·01);治疗组治疗后7周较4周时LVEF值明显好转(BM-MSCs组45·0±2·7比33·6±2·1,Ad5-HGF组43·9±4·3比32·2±1·8,P均<0·01),对照组前后LVEF值无明显变化;两治疗组LVEF值改善幅度相比,差异无统计学意义。结论经非梗死相关动脉移植BM-MSCs或Ad5-HGF均能促进梗死心脏心功能改善和促进血管再生,但未显示出二者之间何者更具优势。
关键词(KeyWords)： 间质干细胞移植;血管内皮生长因子类;心肌梗死;心力衰竭,充血性
基金项目(Foundation): 江苏省自然科学基金(No:RC2002043)
作者(Author): 王连生,王伟,杨志健,马东超,徐顺霖,张郁青,周芳,陈波,曹克将,马文珠
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