活性氧簇在低氧诱导的肺纤维化中的作用

Role of reactive oxygen species in hypoxia-induced pulmonary fibrosis

活性氧簇是一类氧的衍生分子,因其可引起蛋白质、DNA等大分子物质损伤、脂质过氧化,一直被认为是有害因子.近年来研究表明活性氧簇的产生是受精细调节的,并且它能作为第二信使激活细胞内MAPK（ERK1/2、p38MAPK和JNK）、Akt/PKB、JAK-STAT、核因子κB等多条信号通路,参与转化生长因子β1、血小板衍生生长因子、缺氧诱导因子、结缔组织生长因子等多种致纤维化因子的信号转导,调节细胞的增殖、分化、凋亡等生理功能,并与动脉粥样硬化、肝纤维化、肺纤维化等疾病的发生有关.低氧是一个重要的病理过程,可引起细胞损伤、组织炎细胞浸润,并能促进上皮细胞向间质细胞转化、细胞外基质沉积,上调转化生长因子β1、血小板衍生生长因子、缺氧诱导因子、结缔组织生长因子等多种致纤维化因子,故低氧有诱导肺纤维化形成的可能.而低氧又可引起活性氧簇产生增多.本文就活性氧簇在低氧诱导的肺纤维化中的作用作一综述.

Reactive oxygen species（ROS） are derivatives of oxygen, have been considered to be a series of deleterious factors which can induce the damage of protein,DNA and other macromolecules and lipid peroxidation. Recently, it is studied that ROS generation is precisely regulated, and as the second messenger,ROS can activate many intracellular signal pathways such as MAPK （ERK1/2,p38MAPK and JNK） ,Akt/PKB,JAK-STAT,nuclear factor-κB and so on, participate in the signal transduction of many fibrogenic cytokines such as transforming growth factor-β1 ,platelet-derived growth factor,hypoxia-induced factor,connective tissue growth factor and so on,regulate cell proliferation,differentiation and apoptosis, and be related to the occurrence of many diseases such as atherosclerosis, liver fibrosis and pulmonary fibrosis and so on. Hypoxia is an important pathological process,can cause cell damage and infiltration of inflammatory cells, promote epithelial-mesenchymal transition and extracellular matrix deposition, increases many fibrogenic cytokines such as transforming growth factor-β1,platelet-derived growth factor, hypoxia-induced factor, connective tissue growth factor and so on, so hypoxia may induce pulmonary fibrosis. And hypoxia can increase ROS production. This paper reviews the role of ROS in hypoxia-induced pulmonary fibrosis.