细颗粒物致人肺泡上皮细胞炎性反应关键组分及机制探究  

Exploration of critical components for PM_(2.5) induced inflammatory reaction in human alveolar epithelial cells

作　　者：王荣[1,2] 张邱栋 张懿烨 贺红梅 王娜娜 秦蓓[1,2] WANG Rong;ZHANG Qiudong;ZHANG Yiye;HE Hongmei;WANG Nana;QIN Bei(College of Pharmacy,Xi’an Medical University,Xi’an 710021,China)

机构地区：[1]西安医学院药学院,陕西西安710021 [2]西安市多靶协同抗高血压创新药物研制重点实验室,陕西西安710021 [3]西安医学院医学技术学院,陕西西安710021

出　　处：《陕西医学杂志》2024年第1期8-12,共5页Shaanxi Medical Journal

基　　金：国家自然科学基金资助项目(81903288);西安医学院校级科技创新团队建设项目(2021TD03);国家级、省级、校级大学生创新创业训练计划项目(202311840020,121522107,121523020);西安医学院科研能力提升计划项目(2022NLTS070)。

摘　　要：目的:研究细颗粒物(PM_(2.5))不同组分对人Ⅱ型肺泡上皮细胞(A549)增殖的作用及机制。方法:制备PM_(2.5)全颗粒、脂溶性和水溶性组分,观察PM_(2.5)不同组分对A549形态的影响;MTT法评价PM_(2.5)不同组分对细胞增殖的影响;酶联免疫吸附实验(ELISA)检测PM_(2.5)不同组分对炎性因子表达的影响。在PM_(2.5)组分暴露的基础上,给予丝裂原活化蛋白激酶(MAPK)信号通路抑制剂和地塞米松,分别检测A549增殖和炎性因子变化情况,MAPK信号通路相关蛋白的表达。结果:除PM_(2.5)水溶性组分外,PM_(2.5)全颗粒和脂溶性组分均能抑制A549细胞增殖,呈时间和浓度依赖性,染毒24h后二者作用的IC50分别为199.9和142.1μg/ml;二者可显著增加细胞上清液中炎性因子的表达。MAPK信号通路抑制剂(U0126、SB203580、SP600125)和地塞米松可显著增强WPPM_(2.5)和LSPM_(2.5)对A549细胞的抑制作用,抑制WPPM_(2.5)和LSPM_(2.5)致炎性因子表达的增加,促进JNK和ERK1/2的磷酸化。结论:PM_(2.5)对A549细胞活力及炎症的影响主要与其非水溶性组分有关,其机制可能与激活ERK1/2MAPK和JNKMAPK信号通路有关。Objective:To observe the effect and mechanism of different components of fine particulate matter(PM_(2.5))on the proliferation of human typeⅡalveolar epithelial cells(A549).Methods:The whole particles,liposoluble-soluble and water-soluble of PM_(2.5) were prepared,and the effects of different components of PM_(2.5) on the morphology of A549 were observed.MTT assay was used to evaluate the effect of different components of PM_(2.5) on cell proliferation.ELISA was used to detect the effect of different components of PM_(2.5) on the expression of inflammatory factors.On the basis of PM_(2.5) component exposure,MAPK signaling pathway inhibitor and dexamethasone were given to A549,and the changes in proliferation,inflammatory factors and the expression of MAPK signaling pathway related proteins were detected.Results:The whole particles and liposoluble-soluble of PM_(2.5)(WPPM_(2.5) and LSPM_(2.5))can inhibit the proliferation of A549 cells in a time-and concentration-dependent manner and the IC 50 were 199.9,142.1μg/ml,respectively.The inflammatory factors in cell culture supernatants increased significantly after WPPM_(2.5) and LSPM_(2.5) exposure.MAPK signaling pathway inhibitors(U0126,SB203580,SP600125)and dexamethasone significantly enhanced the inhibitory effect of WPPM_(2.5) and LSPM_(2.5) on A549 cells,inhibited the increase in the expression of inflammatory factors induced by WPPM_(2.5) and LSPM_(2.5),and promoted the phosphorylation of JNK and ERK1/2.Conclusion:The effect of PM_(2.5) on A549 cell viability and inflammation was related with water-insoluble components,and the mechanism may be related to the activation of ERK1/2 MAPK and JNK MAPK signaling pathways.

关 键 词：PM_(2.5) A549细胞 细胞毒性 炎症反应 丝裂原活化蛋白激酶信号通路 关键组分 

分 类 号：R364.5[医药卫生—病理学]