脑源性神经营养因子与纤维化疾病的研究进展

Research progress of brain-derived neurotrophic factor in fibrotic diseases

纤维化通常被认为是组织损伤修复过程中促进伤口愈合的产物。机体受到病理刺激损伤后,组织将开始自我修复,及时高效地替换死亡或受损的细胞,这一修复机制是机体最基本、最重要的生物学过程之一。修复过程通常分为再生阶段和纤维增生阶段。首先当细胞受损后,同类型的细胞进行替换,防止损伤持续;其次正常的实质组织可被结缔组织所取代。最初的修复往往是有益的,但一旦失控,愈合过程就会变成病理性损伤,从而导致细胞外基质重构和永久性瘢痕组织的形成[1]。当纤维化发生在重要组织器官时,可能导致器官衰竭甚至死亡。目前,纤维化疾病已占到发达国家总死亡率的45%,带来沉重的医疗负担。然而,迄今为止,只有尼达尼布和吡非尼酮这两种药物被批准在几个国家用于治疗特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)[2]。因此,治疗纤维化疾病的有效药物仍十分匮乏,亟需探索纤维化发生的新机制,筛选有效的治疗靶点并研发新型抗纤维化药物。

Brain-derived neurotrophic factor(BDNF) plays neurotrophic and repair roles by binding to its specific tyrosine kinase receptor B.Recently,studies have found that BDNF is widely expressed in visceral organs and tissues,including heart,lung,liver,kidney,bladder,and participates in the pathophysiological process of many diseases.Organ fibrosis is a serious disease that leads to the damage of its own structure and function,and then causes organ failure and even threatens the life.To date,therapeutic drugs for fibrosis are limited and the effect is not ideal,so it is urgent to find new interventional targets.Growing evidence suggests that BDNF expresses in various fibroblasts and plays important roles in the regulation of fibrotic disorders.This article reviews the source of BDNF,function as neurotrophic factors and the roles of BDNF in different organ fibrosis,to provide new ideas for the prevention and treatment of fibrosis from the perspective of neurotrophic factors.