神经生长因子促大鼠缺血后肢血管再生的实验研究

Promotion of angiogenesis by NGF in ischemic hindlimb circulation

目的:通过制备大鼠后肢缺血模型,我们对神经生长因子(NGF)促大鼠缺血后肢血管再生的功能进行评价,为临床上治疗下肢缺血性疾病提供一些新的思路及实验依据。方法:通过结扎W istar大鼠一侧股动脉制备大鼠缺血后肢模型,通过EL ISA和免疫组化,观察缺血后肢的血管再生与NGF及其高亲和力受体在缺血组织中的表达与是否具有相关性的作用。结果:反复的缺血内收肌的NGF注射,可以增加毛细血管和小动脉的密度,减少血管内皮细胞及纤维细胞的凋亡,并在不改变血流动力学的前提下加速缺血再灌注。结论:结果表明NGF在血管的修复和新生血管的形成中起到很大的作用。此外,在组织缺血的条件下,NGF途径的正反馈作用,刺激了血管再生及动脉形成,从而加速了血液血流动力的恢复,NGF可以促进血管内皮生长因子(VEGF)在缺血肢体骨骼肌中的表达,从而可能促进缺血肢体的血管再生;通过增加一定剂量的NGF,可以明显改善缺血肢体的功能恢复。NFG促血管再生的机制可以做为缺血性血管疾病的治疗的一个科研方向。

Objective：To assess the function of Nerve Growth Factor（NGF） to promote angiogenesis in ischemic hindlimbs in an attempt to provide some new ideas and experimental evidence for the treatment of lower extremity ischemic disease.Methods：Unilateral limb ischemia was produced in Wister rats by femoral artery resection.By ELISA and immunohistochemistry,we investigated the relationship between the ischemic hindlimb angiogenesis and NGF and its high-affinity receptor expression.Results：Repeated NGF injection into ischemic adductors increased capillary and arteriole density,reduced endothelial cell and myofiber apoptosis,and accelerated perfusion recovery,without altering systemic hemodynamics.Conclusion：NGF plays a functional role in reparative neovascularization.Furthermore, in ischemia,the positive feedback of NGF pathway stimulates angiogenesis,thereby accelerating hemodynamic recovery.NGF can promote vascular endothelial growth factor（VEGF）expression in ischemic skeletal muscle to promote angiogenesis in ischemic limbs.By increasing the dose of NGF,functional recovery of ischemic limbs can be significantly improved.NGF might be envisaged as a utilitarian target for the treatment of ischemic vascular disease.