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目的观察阿霉素诱导的低龄扩张型心肌病(dilated cardiomyopathy,DCM)模型鼠心功能和心室肌细胞钠通道的情况,以及骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMMSCs)移植后低龄DCM鼠心功能和钠通道的改变,探讨BMMSCs移植后钠通道对心功能改善的作用。方法 75只14 d龄的雌性SD鼠分为5组:正常组、正常+BMMSCs移植组(正常鼠左室前壁注射BMMSCs)、DCM组、DCM+PBS移植组(DCM鼠左室前壁注射PBS)、DCM+BMMSCs移植组(DCM鼠左室前壁注射BMMSCs),以腹腔注射阿霉素来诱导低龄DCM模型鼠;移植后4周以荧光显微镜观察心肌组织冰冻切片评价BMMSCs植入情况,通过超声心动图和全细胞膜片钳技术对各组大鼠心功能和钠通道功能的变化情况进行检测。结果荧光干细胞示踪检查显示植入的BMMSCs在注射点附近呈团分布或沿进针路径分布,生长良好;超声心动图检查显示DCM组心功能较正常组及正常+BMMSCs移植组降低(P<0.05),DCM+BMMSCs移植组心功能较DCM组及DCM+PBS移植组提高(P<0.05),DCM+BMMSCs移植组移植4周后心功能较移植前提高(P<0.05);膜片钳检查显示DCM组钠电流(sodium channel current,I_(Na))的电流密度峰值较正常组及正常+BMMSCs移植组降低,电流-电压(Ⅰ-Ⅴ)曲线上移,激活减慢,激活曲线右移,失活加快,失活曲线左移,差异具有统计学意义(P<0.05);而DCM+BMMSCs移植组的I_(Na)电流密度峰值较DCM组及DCM+PBS移植组提高,Ⅰ-Ⅴ曲线下移,激活加快,激活曲线左移,失活减慢,失活曲线右移,差异具有统计学意义(P<0.05)。结论 BMMSCs移植能改善低龄DCM鼠的心功能,其机制可能与BMMSCs移植后钠通道功能增强有关。
Objective To observe the changes of cardiac function and ventricular myocytes sodium channels in adriamycin-induced dilated cardiomyopathy (DCM) model rats and the effects of adriamycin-induced small cell infiltration of bone marrow mesenchymal stem cells (BMMSCs) Rat heart function and sodium channel changes to explore the effect of sodium channel on the improvement of cardiac function after BMMSCs transplantation. Methods Seventy-five SD rats aged 14 days were divided into five groups: normal group, normal + BMMSCs transplantation group (normal mice injected BMMSCs), DCM group, DCM + PBS transplantation group PBS) and DCM + BMMSCs transplantation group (BMMSCs were injected into the left anterior wall of DCM rats). Adriamycin was injected intraperitoneally to induce low-age DCM model rats. Four weeks after transplantation, the myocardial tissues were observed by fluorescence microscopy. The changes of cardiac function and sodium channel function in each group were detected by echocardiography and whole-cell patch clamp technique. Results Fluorescent stem cell tracing showed that the implanted BMMSCs were distributed in clusters or along the needle path, with good growth. Echocardiography showed that cardiac function in DCM group was lower than that in normal group and BMMSCs transplantation group (P < (P <0.05). The cardiac function in DCM + BMMSCs transplantation group was higher than that in DCM group and DCM + PBS transplantation group (P <0.05), and the cardiac function in DCM + BMMSCs transplantation group was higher than that before transplantation (P <0.05) The current density peak of sodium channel current (I_ (Na)) in DCM group was lower than that in normal group and normal BMMSCs transplantation group. The current-voltage curve shifted upwards, the activation slowed down, the activation curve moved to the right, The peak of I_ (Na) current density in DCM + BMMSCs transplantation group was higher than that in DCM group and DCM + PBS transplantation group, while Ⅰ-Ⅴ curve (P <0.05) Down, activated to speed up, activation curve to the left, inactivation slowed, inactivation curve shifted to the right, the difference was statistically significant (P <0.05). Conclusion BMMSCs transplantation can improve the cardiac function of young DCM rats. The mechanism may be related to the enhanced function of sodium channels after BMMSCs transplantation.