摘要
百草枯(PQ)中毒引发肺纤维化机制尚未明确,缺乏针对性治疗药物和措施。PQ中毒后,复杂的细胞网络调控肺成纤维细胞大量增殖并分泌细胞外基质,引起肺纤维化,最终导致呼吸衰竭。炎症因子白细胞介素(IL)-6、IL-17和肿瘤坏死因子α可在PQ中毒初期加重肺损伤,促进肺上皮细胞上皮-间充质细胞转化及静息间充质干细胞转化为肌成纤维细胞;促纤维化细胞因子转化生长因子β、结缔组织生长因子、血管内皮生长因子、血小板衍生生长因子、低氧诱导因子1α可通过诱导肺成纤维细胞增殖并大量分泌细胞外基质促进肺纤维化;此外,抗纤维化细胞因子肝细胞生长因子、脂联素、褪黑素和成纤维细胞生长因子21可通过促进受损肺上皮细胞的增殖修复、抗氧化应激、下调促纤维化因子的表达来拮抗纤维化的发生发展。本文对炎性细胞因子、促纤维化细胞因子和抗纤维化细胞因子参与PQ中毒致肺纤维化的机制以及治疗策略进行了综述。
The mechanism of pulmonary fibrosis induced by paraquat(PQ)poisoning is not yet clear,and there is a lack of targeted treatment drugs and measures.After paraquat poisoning,a complex cell network regulates the proliferation of lung fibroblasts which secrete extracellular matrix,causing pulmonary fibrosis and respiratory failure.Inflammatory factors-interleukin-6,interleukin-17 and tumor necrosis factor-α-can aggravate lung injury at the initial stage of paraquat poisoning,promote the epithelialmesenchymal transformation of lung epithelial cells and the transformation of resting mesenchymal stem cells into myofibroblasts.Transforming growth factorβ,connective tissue growth factor,vascular endothelial growth factor,platelet-derived growth factor,hypoxia-inducible factor 1αcan promote lung fibrosis by inducing the proliferation of lung fibroblasts which secrete a large amount of extracellular matrix.In addition,the anti-fibrotic cytokines hepatocyte growth factor,adiponectin,melatonin,and fibroblast growth factor 21 can promote the proliferation and repair of damaged lung epithelial cells,resist oxidative stress,and down-regulate the expression of pro-fibrotic factors to suppress development of fibrosis.This article reviews the mechanisms and treatment strategies of inflammatory cytokines,pro-fibrotic cytokines,and anti-fibrotic cytokines involved in pulmonary fibrosis induced by paraquat poisoning.
作者
孙阳阳
骆媛
王永安
SUN Yang-yang;LUO Yuan;WANG Yong-an(State Key Laboratory of Toxicology and Medical Countermeasure,Institute of Pharmacology and Toxicology,Acadamy of Military Medical Sciences,Beijing 10085,China;Hospital 96604 of PLA,Lanzhou 730030,China)
出处
《中国药理学与毒理学杂志》
CAS
北大核心
2021年第7期551-558,共8页
Chinese Journal of Pharmacology and Toxicology
关键词
百草枯
肺纤维化
细胞因子
paraquat
pulmonary fibrosis
cytokines
