新生儿缺氧缺血性脑损伤中自噬的动态作用及干预价值的研究进展

Research progress on the dynamic role and intervention value of autophagy in neonatal hypoxic-ischemic brain damage

新生儿缺氧缺血性脑损伤(HIBD)后神经系统修复尚无特效疗法,是医学界研究的难点与热点。自噬作为一种细胞自我修复机制,在不同阶段通过不同的信号途径发挥作用,但其在HIBD不同阶段的具体作用和机制尚未完全阐明。本文回顾了近些年有关自噬在新生儿期HIBD不同阶段的研究结果:在缺氧缺血的急性期,自噬活性明显增加,其保护或损伤作用仍存在争议;而在亚急性及慢性期,自噬可能对神经元存在促死亡和神经修复双重作用;在后遗症期,自噬相关研究尚不充分,但脑瘫患儿自噬相关基因(ATG)的表达水平揭示了自噬在HIBD后的正反两面性。从整体研究来看,适度的自噬水平有助于清除受损组分和毒性蛋白,发挥神经保护作用。进一步研究自噬在HIBD中的作用和机制,将有助于开发基于自噬的HIBD防治策略,提高患儿的生存率和生活质量。

The repair of the nervous system after hypoxic-ischemic brain damage(HIBD)in neonates lacks specific therapeutic approaches,posing a challenge and hot topic in the medical field.Autophagy,as a cellular self-repair mechanism,plays a role through different signaling pathways at different stages,yet its specific roles and mechanisms in different stages of HIBD remain unclear.This article reviews the recent research advancements on autophagy in different neonatal HIBD stages:heightened autophagic activity manifests during the acute hypoxic-ischemic phase,with its neuroprotective or deleterious impact subject to ongoing debate;during the subacute and chronic phases,autophagy exert dual effects on neuronal death and repair;in sequelae period,autophagy-related studies are still insufficient,but the expression levels of autophagy-related genes(ATG)in children with cerebral palsy suggest both positive and negative aspects of autophagy post-HIBD.Collectively,optimal autophagic flux facilitates the elimination of detrimental substrates and toxic proteins,thereby engendering neuroprotection.Further studies on the roles and mechanisms of autophagy in HIBD therapy holds promise for devising efficacious preventative and therapeutic strategies rooted in autophagy,and to improve the survival rate and quality of life of the children.