生长因子修复脊髓损伤的疗效及其机制

The Roles of Growth Factors in Spinal Cord Injury

脊髓损伤(spinal cord injury,SCI)是神经系统最严重的创伤之一,其所造成的高致残率和严重并发症,给个人、家庭和社会均造成巨大负担。脊髓损伤后,由于原发性损伤和继发性损伤等一系列病理变化,使轴突再生和受损神经元的重塑变得非常困难,其中微环境的紊乱是导致二次损伤恢复的主要障碍。脊髓损伤治疗的药物选择对于其预后有较大影响。其中,生长因子(growth factors,GFs)在中枢神经系统发育与损伤修复中具有重要的调控作用。目前,利用GFs干预治疗锯齿动物SCI后的结构和功能恢复方面,包括神经发生、轴突生长、神经保护和再生,促进血管生成、组织修复、保护内源性神经干细胞等方面已取得较为满意的效果,为SCI的临床治疗提供了良好的应用前景。随着对GFs的研究深入,单一的GFs难以满足脊髓损伤后复杂的生理病理变化。因此,探索多种GFs的联合应用以期达到协同的神经再生和功能恢复,是目前治疗SCI的重要策略之一。由于GFs是大分子蛋白质类药物,存在半衰期短,以及原位注射在损伤部位易流失等缺点限制了GFs的临床应用。因此,很多研究将GFs结合不同生物材料治疗SCI,以此克服GFs本身的缺陷,并进一步延长该类药物的修复效果。本综述归纳总结了几种典型的GFs对SCI修复的研究进展和可能的作用机制,并展望不同的生物材料结合GFs提高SCI修复效果的未来发展前景。

Spinal cord injury(SCI),one of the most serious injuries to the nervous system,causes high disability rates and serious complications that poses severe financial burdens on individuals,families and society.The pathology of SCI can be divided into the primary injury and the secondary injury.Those two pathological phases,especially for the secondary phase of injury,are the main cause for the microenvironment imbalance which seriously affects axonal regeneration and neuronal remodeling.Several therapeutic drugs have been listed as the neurorestorative candidates for SCI treatment.Among them,the application of growth factors(GFs)as a therapy to improve morphological and behavioral outcomes after SCI has drawn extensive attention due to their benefit on exerting neurogenesis,axonal growth and neuroprotection,promoting angiogenesis and tissue repair,mobilization of endogenous neural stem cells to facilitate structure and function recovery.To counter multiple injury mechanism and target different types of cells in the injured spinal cord,several researchers have attempted to investigate the various combinations of GFs for SCI treatment.Nevertheless,as the macromolecular proteins,GFs application is limited due to their short half-life and rapid diffusion from the injected site after in-situ injection.To extend the in vivo efficacy,numerous strategies incorporate the GFs into biocompatible and biodegradable biomaterials which is expected to achieve its controlled release over an extended time.This review focuses predominantly on the therapeutic effect of a few typical GFs on SCI repair and their underlying molecular mechanisms,and finally provides perspectives for the combination of GFs and biomaterials together for enhancing therapeutic efficacy on SCI repair.