兔骨髓间充质干细胞自体移植对缺血心肌心功能的影响

Effects of autologous transplantation of bone marrow mesenchymal stem cells on heart function of ischemic myocardium in rabbits

目的 :了解骨髓间充质干细胞 (MSCs)在心肌梗死 (MI)的缺血心肌微环境中转化为心肌细胞并改善心功能的可行性。方法 :结扎兔左前降支制作急性MI模型 ,骨穿抽取骨髓 ,分离培养扩增MSCs ,其中一组于培养基中加入 5 氮胞苷 (5 aza) 10 μmol/L。术后 2周进行MI瘢痕内移植 5 溴脱氧尿嘧啶 (BrdU)标记的MSCs,对照组注射培养基。MI术前、术后 3d及移植后 4周做超声心动图检测心功能 ,移植后 4周从右颈总动脉插管至左心室测左室压力变化 ,随后处死动物取左室标本作冰冻切片 ,采用免疫荧光方法鉴定植入细胞。结果 :细胞移植组左室切片中均可见BrdU染色阳性细胞即植入细胞 ,对照组未见BrdU染色阳性细胞。超声心动图检测证实移植后 4周细胞移植组左室收缩末期直径、舒张末期直径均小于对照组 (分别为P <0 .0 1及P <0 .0 5 ) ,小轴缩短率、射血分数均大于对照组 (均P <0 .0 1)。导管测压显示细胞移植组的左室舒张末期压低于对照组、左室压上升及下降最大速率高于对照组 (均P <0 .0 1)。加 5 aza细胞移植组与不加 5 aza组上述各指标差异无统计学意义。结论 :缺血心肌内注射MSCs可依赖组织微环境转化为心肌细胞修复梗死心肌 ,显著改善心功能 ,可用于MI的治疗。

Objective: To investigate the feasibility that bone marrow mesenchymal stem cells (MSCs) differentiate into cardiomyocytes in ischemic myocardium microenvironment and whether they improve heart function. Method: The left anterodecendant arteries (LAD) of adult rabbits were ligated so as to establish animal models of acute myocardial infarction. MSCs were isolated from bone marrow and were cultured in cell medium or medium with 5-azacytidine(5-aza, 10 μmol/L). 2 weeks later the expanded MSCs labeled with BrdU were injected into the scar tissue. The heart function of each rabbit was measured by echocardiography and hemodynamics. Specimens were taken 4 weeks after implantation. Histologic sections of left ventricular were stained by immunofluorescent and examined under fluorescent microscope. Result: The implanted cells were found in both groups and not in the control group. Compared with control group, 4 weeks after implantation two transplanted groups result in shorter LVESD ,LVED Dandh igherEF ,△D % ,±dp/d tmax an dlow erLVEDP .There is nosignifican cebetwee nthegroup with 5 azaan dthe groupwi thout 5 aza .Conclusion :A utologo usbonema rrowmesenchymalstemcellscandifferentiate intoc ardiomyo cytesinvivotore pairinf ractedmyoca rdi umandim prov ethehear tfunction .Bone marrowMS Cstrans plan tati oncanused to therapy acute myocardial infarction .