AIM:To investigate the therapeutic effects of recombinant meglumine cycle adenylate phosphate ( MCA) and bone marrow mesenchymal stem cells ( BMSCs ) on the enhancement of the cell survival and improvement of the cardiac functions in the rat model of adriamycin - induced cardiomyopathic heart failure. METHODS:BMSCs were I-solated and expanded using the pre - plating method. Doxorubicin was used by intraperitoneal injection into the Wistar rats to establish the model of cardiomyopathic heart failure. The model animals randomly received the injection of PBS, MCA, BMSCs or MCA + BMSCs respectively, and normal controls were without any treatment. Four weeks after injection, the cardiac functions were determined by echocardiography and multichannel physiological recorder. The levels of brain natriuretic peptide ( BNP) were measured by ELISA. The positive rate of BrdU - labeled BMSCs in the myocardium was analyzed by the method of immunohistochemistry. The expression of myocardium - specific protein, GATA -4, connexin 43( Cx43 ) and cardiac troponin l( cTNI), was detected by Western blotting.Myocardial fibrosis was observed with Masson's staining.RESULTS : Compared with other groups, the results of echocardiography and hemodynamic showed that the left ventricular functions in BMSCs + MCA group improved significantly ( P < 0. 05 ). The BMSCs numbers in the myocardium in BMSCs + MCA group were significantly higher than those in BMSCs group ( P <0. 05 ). The level of BNP was significantly lower in BMSCs + MCA group than that in BMSCs group ( P <0. 05 ). Compared with other groups, the expression of GATA - 4, Cx43 and cTNI was significantly increased in BMSCs + MCA group. CONCLUSION: Combination of MCA with BMSCs transplantation improves the cardiac functions, possibly due to the enhancement of BMSCs survival and the increase in the protein expression of GATA -4.%目的:研究环磷酸腺苷葡甲胺(MCA)对骨髓间充质干细胞(BMSCs)移植在心肌组织存活和对心力衰竭(HF)大鼠心功能的影响.方法:贴壁法体外分离、扩增培养大鼠BMSCs;采用阿霉素腹腔注射方法建立心力衰竭大鼠模型,随机分为正常组、HF组、BMSCs组、MCA组和BMSCs+MCA组.BMSCs经尾静脉注射1次,MCA经尾静脉连续注射5 d.4周后通过超声心动图和多导生理记录仪评价心功能.ELISA法测定干预前后脑利钠肽(BNP)浓度变化.免疫组化观察BrdU标记BMSCs在心肌内的阳性率,Western blotting测定心肌特异性蛋白GATA-4、缝隙连接蛋白43(Cx43)和心肌肌钙蛋白I(cTnI)的表达,Masson染色观察心肌纤维化改变.结果:心脏超声心动图和血流动力学结果显示,BMSCs+MCA组大鼠的左室收缩功能各项指标明显优于其它组(P<0.05);而MCA组与BMSCs组相比心功能改善无明显差异(P＞0.05).干预后BNP水平比较,BMSCs+MCA组与BMSCs组差异显著(P<0.05).与BMSCs组相比,BMSCs+MCA组心肌组织切片上BrdU标记的BMSCs阳性细胞数量增多(P<0.05),GATA-4、Cx43和cTNI表达增多,纤维化程度减轻.结论:单纯BMSCs移植与MCA药物治疗相比对心功能的改善没有明显益处.而MCA和BMSCs移植联合则可提高BMSCs存活率,增加GATA-4等蛋白表达,改善心脏收缩和舒张功能.
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