补充外源性神经生长因子对大鼠心肌梗死后延迟再灌注的影响

Effects of Exogenous Nerve Growth Factor on Late Reperfusion after Myocardial Infarction

探讨外源性神经生长因子(NGF)在大鼠心肌梗死后延迟再灌注治疗中的作用及机制。通过建立大鼠心梗延迟再灌注模型,构建重组腺病毒Ad-NGF基因并进行基因转染,使大鼠心梗延迟再灌注后体内NGF持续高表达。在术后第3、7、和/或14、28天检测NGF蛋白表达、微血管增生数量,观察心肌细胞凋亡情况、心脏结构及功能的变化。我们发现,给予NGF治疗的过表达组,NGF各时间点含量均高于对照组(P<0.01),凋亡率均低于模型对照组(P<0.01或P<0.05);过表达组新生微血管数量在第14天、28天明显高于模型对照组(P<0.01,P<0.05)。超声心动图记录第28天时模型对照组左室舒张/收缩末期内径测值明显高于过表达组(P<0.05),左室舒张/收缩末期容积测值明显高于过表达组(P<0.01),即模型对照组心脏结构改变明显;第14天和第28天时过表达组左室射血分数、短轴缩短率均明显高于模型对照组(P<0.01),即过表达组心功能较模型对照组明显改善。因此我们认为,外源性NGF通过促进血管增生和抑制心肌细胞凋亡等途径改善了大鼠心肌重塑及心脏功能。

This study demonstrates that nerve growth factor （NGF） plays a protective role in myocardial infarction and early reperfusion by reducing the myocardial cell apoptosis and by improving ventricular remodeling and seeks to assess the effects and mechanisms of NGF on late reperfusion after myocardial infarction. The models of late reperfu- sion were established by ligating the left main coronary artery and then cutting the suture 2 hours after coronary ar- tery Iigation. The rats in NGF treatment group were injected 10 ~L Ad NGF （by constructing the adenovirus vector A＆NGF containing NGF gene） at four locations around infarction. The rats in adenoviral vector （Adv） group were injected 10 I^L adenoviral cector as the NGF group. The late reperfusion group and the sham group were given nor- mal saline as above, and the sham group underwent thracotomy without coronary ligation. On the 3rd, 7th, 14th and 28th day after operation, we investigated the role of NGF on late reperfusion by recording cardiac structure and func- tion with echocardiography, by examining the expression of NGF and ~ factor with immunohistochemical method, and by evaluating the myocardial cell apoptosis with terminal dUTP nick endqabeling method （TUNEL）. We found that the NGF group had higher expression of NGF protein （P〈0.01） and lower apoptosis index （AI） （P〈0.01 or P〈0.05） compared to the late reperfusion group and Adv group on all time points. The NGF group had remarkably higher level of neovascularization compared to the late reperfusion group on the 14th day （P〈0.01） and the 28th day （P〈0. 05）. The NGF group also had higher LVEF and FS levels compared to the late reperfusion group on the 14th day （P=0.006, P=0.006） and on the 28th day （P=0,000, P〈0.000）. Whereas the NGF group had lower LVEDD, LVESD （P=0.038, P=0.000） and lower LVEDV, LVESV （P=0.001, P=0.000） on the 28th day compared to late reperfusion group. In this experiment, the NGF gene carried by adenovirus vector had been transfected and obviously increased the expression of NGF protein in NGF group. NGF may help postpone the myocardial remodeling and improve the heart function by promoting the myocardial neovascularization and inhibiting myocardial apoptosis.