5-氮胞苷诱导自体骨髓单个核细胞移植对心功能的影响

Effects of bone marrow mononuclear cell implantation induced by 5-azacytidine on cardiac function

目的 观察骨髓单个核细胞 (BM MNC)经化学诱导剂 5 氮胞苷诱导后 ,移植到梗死心肌边缘 ,能否进一步改善心功能。方法 2 6只雄性家兔 ,随机选取 2 1只结扎冠状动脉左前降支 ,建立急性心肌梗死 (AMI)模型 ,随机分为BM MNC +5 氮胞苷组、BM MNC组和AMI未治疗组 3组 ,每组 7只 ;其余 5只为假手术对照组。AMI后第 3d抽取自体股骨骨髓 1 5ml,分离单个核细胞培养 ;AMI后 14d将培养的单个核细胞移植至梗死心肌边缘 ;移植 2 8d后 ,采用超声心动图 ,并结合左心导管、血流动力学等参数评价心功能情况。结果 AMI后兔心功能明显受损 ,与假手术对照组相比 ,AMI后各组左室舒张末期压明显升高 (P <0 0 5 ) ,左室短轴缩短率、左室壁厚度、射血分数、左室收缩压、压力变化率最大值显著降低(P <0 0 5 )。细胞移植后 ,与AMI未治疗组相比 ,细胞移植组左室舒张末期压显著降低 ,左室短轴缩短率、左室壁厚度、射血分数 ,以及左室收缩压、压力变化率最大值明显升高。但 5 氮胞苷诱导的骨髓单个核细胞移植组与未经诱导组间各项指标差异无显著性。结论 5 氮胞苷诱导的骨髓单个核细胞移植能明显改善心功能 ,并防止AMI后左室重构发生 ;但与单纯骨髓单个核细胞移植相比差异无显著性。

Objective: Recent studies have shown that cell implantation can replace infarcted myocardium to improve cardiac performance. The present study was designed to investigate the effects of autologous bone marrow mononuclear cell (BM-MNC) implantation into myocardium bordering the infarction with or without induced by 5-azacytidine on cardiac function after acute myocardial infarction (AMI) in rabbits. Methods: AMI was replicated by ligating the left anterior descending coronary artery. Rabbits were randomly divided into three groups: (1) BM -MNC induced by 5-azacytidine implantation (n=7), (2) BM-MNC implantation alo ne (n=7), and (3) AMI control (n=7). In addition, sham-operated (n=5) rabbit s were randomly selected to serve as non-infarction control. Animals for cell im p lantation were received intramyocardial injection of autologous BM-MNC in myoca rdium bordering the infarction, and echocardiography and hemodynamic studies wer e performed to evaluate cardiac function following 28 days of implantation. Results: Compared with the sham-operated group, the left ventricle (LV) end diastolic pressure (LVEDP) was significantly increased (P<0.05) in all AMI procedure groups. The ΔD (Dd minus Ds) to Dd ratio (ΔD/Dd), wall thickness, ejection fraction (EF), left ventricle systolic pressure (LVSP) and maximum LV pressure rising rates (dp/dtmax) were all significantly reduced (all P< 0.05). These changes indicated LV remodeling occurred and LV function were impaired. Comparison among all AMI procedure groups showed that impaired LV function were improved by autologous BM-MNC implantation, as revealed by decreased LVEDP (BM-MNC implantation vs. AMI alone, P<0.05) and increased ΔD/Dd, wall thickness, EF, LVSP, and dp/dt max (BM-MNC implantation vs. AMI alone, all P<0.05). Furthermore, BM-MNC induced by 5-azacytidine implantation did not confer a further improvement of cardiac function with non-significant changes of all assessed parameters when compared with BM-MNC implantation alone (all P>0.05). Conclusion: BM-MNC induced by 5-azacytidine implantation into myocardium bordering the infarction can significantly improve impaired cardiac function associated with LV remodeling after AMI, however such improvement is not further promoted compared with that in BM-MNC implantation group alone.