百草枯中毒致肺纤维化信号通路研究进展

Progress in the study of pulmonary fibrosis signaling pathways caused by paraquat poisoning

百草枯是一种季铵盐除草剂,可经血液循环分布于肺、肝、肾、心、脑等器官,导致多器官功能衰竭,其中以肺损伤最为显著。由于缺乏有效的治疗手段及特效解毒药物,临床上大多数百草枯中毒患者预后极差,百草枯中毒的救治疗成为目前急诊医生面临的一大难题。氧化应激、炎症反应、线粒体损伤、细胞外基质(ECM)的生成和降解失衡等多种病理过程与百草枯中毒导致肺纤维化有密切关系。近年来,许多研究者着力于阐明百草枯中毒导致肺纤维化的机制,表明信号转导在百草枯导致的肺纤维化中起重要作用,本文就腺苷酸活化蛋白激酶(AMPK)、转化生长因子-β(TGF-β)相关的TGF-β/Smad信号通路、丝裂素活化蛋白激酶(MAPK)相关信号通路、Ras同源基因/Rho相关激酶(Rho/ROCK)信号通路、Wnt/β-连环蛋白(Wnt/β-catenin)信号通路与百草枯致肺纤维化的关系进行综述,以期为临床治疗百草枯中毒导致的肺纤维化提供更多思路。

Paraquat is a quaternary ammonium herbicide,which can be distributed in lung,liver,kidney,heart,brain and other organs through blood circulation,leading to multiple organ failure,especially lung injury.Due to the lack of effective treatment methods and specific antidotes,the prognosis of most patients with paraquat poisoning is very poor.The treatment of paraquat poisoning was a big problem for emergency doctors.Previous studies have found that pulmonary fibrosis caused by paraquat poisoning is closely related to a variety of pathological processes,such as oxidative stress,inflammatory reaction,mitochondrial damage,imbalance of extracellular matrixproduction(ECM)and degradation,which involve the activation or inhibition of various signaling pathways.In recent years,many researchers focused on clarifying the mechanism of paraquat induced pulmonary fibrosis,and some signaling pathways related to paraquat poisoning leading to pulmonary fibrosis have been found.A large number of studies have found that adenosine monophosphate activated protein kinase(AMPK)related signaling pathway,transforming growth factor-β/Smad(TGF-β/Smad)signaling pathway,mitogen-activated protein kinase(MAPK)related signaling pathway,Ras homolog gene/Rho associated kinases(Ras/ROCK)and Wnt/β-catenin signal pathways are closely related to paraquat induced pulmonary fibrosis.In this paper,we reviewed signaling pathways related to paraquat induced pulmonary fibrosis,in order to provide more ideas for the clinical treatment of paraquat induced pulmonary fibrosis.