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目的 研究肝细胞生长因子(HGF)对大鼠供体心长时间保存的保护作用并探讨其可能作用机制.方法 40只SD大鼠随机分为对照组(n=20)和实验组(n=20).Langendorff-Neely灌注模型.分别用HTK液和HTK+rh-HGF(100 μg/L)液作为停跳液和保存液,保存8 h(A组,C组)和12 h(B组,D组).通过检测保存前后的血流动力指标的恢复率;测定冠脉流出液中CK、LDH,NO、ET的变化;免疫组化测定c-met;TUNEL法检测AT;RT-PCR法检测心肌bcl-2 mRNA的表达.结果 实验组血流动力学指标恢复较好(P＜0.01),心肌病理损伤减轻;冠脉流出液中CK,LDH含量降低(P＜0.01),NO活性提高(P＜0.05);ET降低(P＜0.01);c-met表达升高(P＜0.01);AI降低(P＜0.01);bcl-2 mRNA的表达升高(P＜0.01).结论 HGF通过其特异性受体c-met的表达改善内皮功能,增加冠脉流量及心肌血流灌注;上调bcl-2表达,减轻供心长时间保存过程中的细胞凋亡,产生有效的保护作用.

Objective To observe the effect of hepatocyte growth factor on preserving isolated heart of rats. Methods Forty rats were random divided into two groups: Control group(n=20)which rat hearts were isolated and preserved in 4℃HTK solution, and experimental group(n=20)which rat hearts were isolated and preserved in 4℃ HTK+rh-HGF(100μg/L)solution. Before operation and rat hearts were subjected to 8 hours(groupA,C)or 12 hours(group B,D)hypothermic storage followed by 5 minutes of normothermic reperfusion onmodified Langendorff-Neely model. The recovery rate of cardiac function after myocardial preservation, such as LVSP and LVDP and±dp/dt max and the changes of CK,LDH,NO and ET were measured. Cell apoptosis was detected by TUNEL staining and the expression of c-met was analyzed by immunohistochemical method. The expression change of bcl-2 mRNA was examined by RT-PCR. Results Compared with control group, experimental group showed that a significantly higher recovery rate of LVSP,LVDP and±dp/dt max(P＜0.01) and lower rate of TUNEL positive cardiomyocytes(P＜0.01) after reperfusion. The leakage of CK and LDH was significant lower than that of control group(P＜0.01). Immunohistochemical analysis revealed that c-met receptor expression was stronger in the HGF-treated myocardium than that in the non HGF-treated myocardium after storage, and this was associated with a stronger expression of bcl-2 mRNA. Conclusion The administration of rh-HGF before storage improved cardiac function after prolonged myocardial preservation by preventing apoptosis and enhancing expression of bcl-2 mRNA. Thus, the addition of rh-HGF in the storage solution may be a promising strategy for prolonged heart graft preservation.