骨髓间充质干细胞移植对心肌梗死大鼠左心功能的影响

Effect of bone marrow stem cells transplantation on heart function of acute myocardial infarction rats

目的研究不同途径和不同浓度的骨髓间充质干细胞(MSCs)移植对心肌梗死大鼠左心功能的影响。方法结扎左冠状动脉前降支制备大鼠心肌梗死模型,采用同种异体大鼠MSCs体外分离、纯化、扩增,4’,6-二脒-2-苯基吲哚(DAPI)标记,将48只SD大鼠随机分为6组,A、B、C和D组于心肌梗死后2周经尾静脉移植MSCs(A组:细胞数5×105、B组:细胞数1×106、C组:细胞数5×106、D组:细胞数1×107),E组:经心外膜注射MSCs(细胞数5×106),对照组:注入等量培养基。4周后测定左心功能并行免疫组织化学检测。结果(1)经静脉和心外膜注射移植MSCs大鼠心肌组织中均可以观察到DAPI标记细胞存在,免疫组织化学阳性标记细胞α-肌动蛋白检测阳性,与对照组比较,两组左心功能均明显改善(P<0.05)和梗死面积均明显缩小[分别为(45±2)%,(40±4)%和(41±3)%,P<0.05]。(2)与对照组比较,A组左心功能无明显改善(P>0.05),B、C、D组左心功能明显改善(P<0.05),C和D组优于B组(P<0.05)。结论MSCs经不同途径归巢至心肌梗死区,改善心功能。

Objective To investigate the effect of bone marrow stem cells （MSCs） transplantation at different concentrations on heart function of acute myocardial infaretion（AMI） rats. Methods AMI was created by occluding the left anterior descending artery （LAD） in SD rats. MSCs of healthy rats were isolated, purified, amplified and labeled with 4＇ ,6-diamidino-2-phenylindole （DAPI）. Forty- eight rats were randomized to six groups. Two weeks after MI, the labeled MSCs were transfused to AMI rats through caudal vein at dosage of 5 ×10^5（A）,1×10^6（B）,5×10^6（C） and 1×10^7（D）, 5×10^6 MSCs were injected via epicardium for group E and culture medium of the same volume was transfused to control group. By the end of the fourth week, the heart functions were evaluated and immunohistochemical analysis was performed. Results The labeled cells were viable in the host hearts and immunochemical staining revealed that the engrafted stem cells expressed α- actin. There was significant difference in left ventricular function and infarction area in groups C and E compared with control group the infarction areas of groups C, E and control group were[ （41 ± 3） %, （40 ± 4） % and （45 ± 2） %, P 〈 0.05]. Compared with that of control group, the left ventriclar function had no difference in group A and was more obviously improved in groups B, C, D and E （ P 〈 0.05）. Among the transplantation groups, the groups C and D had greater improvement than group B （ P 〈 0.05）. Conclusions MSCs can migrate into the infarcted areas through different ways and improve the heart function.