骨髓间充质干细胞治疗心肌梗死后心功能衰竭的远期疗效  

The Prostecdtive Efficacy of Mesechymal Stem Cells Transplantion on InfarctionInduced Heart Failure of Rats

作　　者：徐瑾[1] 王彬尧[1] 何奔[1] 王长谦[1] 陈颖敏[1] 李慧丽[1] 

机构地区：[1]上海交通大学医学院附属仁济医院心内科,上海市200001

出　　处：《中国动脉硬化杂志》2006年第7期585-589,共5页Chinese Journal of Arteriosclerosis

基　　金：上海市自然科学基金(02ZB14038)

摘　　要：目的采用2’脱氧5-氮杂胞苷诱导的骨髓间充质干细胞移植于心肌梗死后心功能衰竭大鼠心肌中,评价其存活、分化及对心功能的保护作用,并研究其慢性演变。方法体外培养的Wistar大鼠骨髓间充质干细胞,用0.3μmol/L的2’脱氧5-氮杂胞苷体外两次诱导第二代骨髓间充质干细胞,并用溴氮胞苷标记后植入心肌梗死10天心功能衰竭大鼠的心肌疤痕中,同时以注射无血清培养基的实验动物为对照。移植前及移植后1、2、3个月通过心脏射血分数等指标评价其对心功能的保护作用,同时通过双重免疫组织化学及电镜观察对移植细胞的存活和分化进行3个月的慢性动态观察。结果移植后1个月,骨髓间充质干细胞移植组大鼠射血分数(83.3%±8.1%,n=13)高于无血清培养基移植组(47.2%±11.8%,n=12)(P<0.01);并且细胞移植组移植后较移植前心功能(64.3%±10.4%)也有改善(P<0.01)。细胞移植组移植后第2个月(射血分数为83.1%±14.4%,n=7)、第3个月(射血分数为86.3%±3.7%,n=6)心功能改善情况继续保持,与无血清培养基移植组第2个月(射血分数为51.6%±11.2%,n=6)、第3个月(射血分数为49.1%±7.7%,n=6)差异均有显著性(P<0.01)。移植的骨髓间充质干细胞在心肌及疤痕中存活,双重免疫组织化学证实其溴氮胞苷及肌钙蛋白T均阳性。电镜观察提示移植后1个月其在疤痕中具心肌样细胞部分特点,但分化细胞核大浆少,未形成明显肌小节及Z带;移植后3个月,可见明显Z带样结构。结论经2’脱氧5-氮杂胞苷诱导的骨髓间充质干细胞可改善心肌梗死后心功能衰竭大鼠的心功能,并能长期保持(观察3个月);其能在心肌梗死后心功能衰竭大鼠心肌及疤痕中存活,并能逐渐向心肌细胞分化。Aim To investigate the survival and differentiation of mesechymal stem cells （MSC） in infarcted myocardium induced by 5-aza-2＇-deoxycytidine（5-aza-CdR） and their effects on infarction-induced heart failure of mrs. The chronic development was also studied. Methods MSC of Wistar rat were cultured in vitro and the second passage MSC were incubated together with 5-aza-CdR （0.3μnol/L） for twice. Then the induced MSC labeled with bromodeoxyuridine （BrdU） were transplanted into the infarcted myocardium of rats in the model of infarction-induced heart failure. The rats receiving serum-free medium injection were used as controls. Before transplantation and 1, 2, 3 month （s） after transplantation, the parameters of heart function, such as ejection fraction （ EF）, were examined by echocardlography and the survival and differetiation of transplanted MSC were observed by double-lable immunohistochemistry and electric microscope. Chronic changes were observed for 3 months. Results One month after transplantation, theEFvalueof MSC transplantedgroup（83.3%±8.1%,n=13）was higher than that of control group （ 47 . 2 %±11. 8 % , n=12） （P〈0.01）. The heart function of MSC transplanted group was also improved compared with that before transplantation { EF = 64.3 % ＋ 10.4%, P 〈 0.01 }. The heart function of MSC trans- planted group sustained during 3 months＇ observation. The EF value was 83.1% _＋14.4% {n=7} and86.3%＋-_3.7% （n= 6} respectively 2 and 3 months after transplantation. While in serum-free medium transplanted group, the EF value was 51.6% ＋_11.2% {n=6} and49.1%-＋7.7% {n=6} respectively 2 and 3 months after transplantation. There was significant differ- ence between two groups 2 and 3 months after transplantation （ P 〈 0.01 ）. The Transplanted cells were survival in myocardial sear. Double-lable immunohistochemistry showed that BrdU and TroponinT of them were positive. Electric microscope showedthat they had some peculiarity of cardiomyoeytes 1 month after transplan

关 键 词：内科学 骨髓间充质干细胞 2'脱氧5-氮杂胞苷 细胞移植 心肌梗死 心功能衰竭 慢性实验 

分 类 号：R5[医药卫生—内科学]