柔毛水杨梅一个新成分促大鼠心肌再生效果及其治疗心肌梗死的初步研究

Myocardial regeneration and repair of infarcted heart by a new composition isolated from Geum japonicum

目的 通过建立大鼠心肌梗死模型,探讨柔毛水杨梅的活性部位促进心肌再生的治疗效果.方法 通过体内、体外生物活性导向的方法从中约柔毛水杨梅分离出促间充质干细胞向心肌分化的有效部位,作为治疗心肌梗死的成分,标记为心肌修复组分（HRF）.将证实具有相似程度左心室梗死的20只实验大鼠分成治疗组和对照组,治疗组（n=10）予HRF灌胃（20 mg·kg-1·d-1）,对照组（n=10）予等量水灌胃,灌胃4周.用超声心动描记术评估心脏功能,Masson三色染色法计算心肌梗死面积及免疫组化双染色法确定心肌梗死区是否有新再牛的心肌细胞.结果 治疗第2周,给药组的左心室射血分数[（66.2±6.9）%比（55.7±6.0）%,P〈0.01]和左心室短轴缩短分数[（46.8 ±5.8）%比（36.4±5.2）%,P〈0.01]均明显高于对照组（P〈0.01）,4周后检测改善效果仍然明显（P〈0.01）.治疗组4周后,心肌梗死面积相对芹心室总面积的百分比为19.O%±6.1%,明显低于对照组的31.1%±8.6%（P〈0.01）,并在心脏的梗死区内发现大量心肌细胞再生.结论 中药柔毛水杨梅中分离出的这个全新的有效组分可以治疗心肌梗死,从而为治疗心肌梗死开辟了新方法.

Objectives To isolate the cardiogenic fraction, which can enhance cardiogenic differentiation of bone marrow-derived mesenchymal stem cells（MSC）from Geum iaponicum.The therapeutic effeet of the isolated cardiogenic fraction was further tested in a rat myocardial infaretion （MI）model.Method Bioassay guided fractionation method was used for the isolation of the cardiogenic fraction,named as heart repair fraction（HRF）.MI was induced by a permanent ligation of left anterior descending coronary artery.The rats exhibiting similarly decreased values of left ventricle ejection fraction（LVEF） and fraction shortening（LVFS）were used.The rats in test group（n=10）were subject to HRF treatment（20 mg·kg-1·d-1）through gastric gavage daily for 4 weeks.Water alone（2 ml/d） was given through gastric gavage to rats in the control group（n=10）.The cardiac function was assessed by echocardiography at different time points.Masson trichrome staining was used for evaluation of the infarct size.Morphological and immunohistochemical studies were performed to investigate the HRF mediated myocardial regeneration.Results LVEF（66.2%±6.9%）and LVFS（46.8%±5.8%）were significantly increased two weeks post HRF treatment compared with the values（LVEF：55.7%±6.0%and LVES：36.4%±5.2%）in control rats（a11 P〈0.01）.The improved heart function was further restored 4 weeks post HRF treatment（P〈0.01）.Furthermore,the treatment of acute MI with this HRF significantly reduced the infarct size（19.0%±6.1%）compared with that（31.1%±8.6%）in control rats（P〈0.01）.Substantial regeneration of cardiomyoeytes in infarcted region of the HRF treated heart was also observed that replaced a considerable part of the infarcted heart tissues resulting in remarkable reduction of the infarct size.Conclusion The properties of this HRF isolated from Geum japonicum in stimulating substantial regeneration of myocardium in infarct region with consequently improved cardiac function appear to be new and represent a new approach for the treatment of MI.