细颗粒物毒性组分对血管平滑肌细胞增殖的影响及其机制研究  

Effect and mechanism of toxic components of fine particulate matter on proliferation of vascular smooth muscle cells

作　　者：王荣[1,2,3] 王娜娜[1,2,3] 张懿烨[3] 陈倩[3] 杨宽 秦蓓 WANG Rong;WANG Nana;ZHANG Yiye;CHEN Qian;YANG Kuan;QIN Bei(Xi’an Medical University,Xi’an 710021,China)

机构地区：[1]西安医学院西安市多靶协同抗高血压创新药物研制重点实验室、西安市智创抗高血压药物国际科技合作基地,陕西西安710021 [2]西安医学院药物研究所,陕西西安710021 [3]西安医学院药学院,陕西西安710021

出　　处：《陕西医学杂志》2024年第7期867-872,共6页Shaanxi Medical Journal

基　　金：国家自然科学基金资助项目(81903288);陕西省重点研发计划项目(2021ZDLSF03-05);西安医学院校级科技创新团队项目(2021TD03);西安医学院大学生创新创业训练计划项目(121523020);教育部产学合作协同育人项目(202101021043,220605634241456)。

摘　　要：目的:探究细颗粒物(PM_(2.5))不同组分对血管平滑肌细胞(VSMCs)增殖的影响及其机制。方法:分别制备PM_(2.5)完全颗粒物、脂溶性组分颗粒物和水溶性组分颗粒物,将VSMCs与PM_(2.5)不同组分染毒液和丝裂原活化蛋白激酶(MAPK)信号通路抑制剂共培养,噻唑蓝比色法(MTT)评价PM_(2.5)不同组分对VSMCs存活的影响;酶联免疫吸附法(ELISA)测定PM_(2.5)不同组分对VSMCs上清液中炎性因子表达的影响;免疫荧光法检测VSMCs中MAPK相关蛋白的表达情况。结果:PM_(2.5)全颗粒(WPPM_(2.5))和脂溶性组分(LSPM_(2.5))对VSMCs存活具有抑制作用,其作用24 h的半数抑制浓度(IC_(50))值分别为178.3μg/ml和283.9μg/ml。LSPM_(2.5)可显著增加白细胞介素-8(IL-8)的表达,U0126、SB2035850和SP600125均能显著降低LSPM_(2.5)增加的IL-8含量,可拮抗WPPM_(2.5)和LSPM_(2.5)对VSMCs的抑制,增加细胞存活率。WPPM_(2.5)和LSPM_(2.5)能激活VSMCs中P38、氨基末端激酶(JNK)和细胞外调节蛋白激酶(ERK1/2)信号通路,使其磷酸化蛋白表达增加。结论:PM_(2.5)可通过激活MAPK炎性信号通路抑制VSMCs增殖,该过程主要与其全颗粒和脂溶性组分有关。Objective:To investigate the effect of typical toxicity of fine particulate matter(PM_(2.5))on the proliferation of vascular smooth muscle cells and its mechanism.Methods:The whole particles,liposoluble-soluble and water-soluble PM_(2.5) were prepared respectively.Vascular smooth muscle cells(VSMCs)were co-cultured with different components of PM_(2.5) and mitogen-activated protein kinase(MAPK)signaling pathway inhibitors.The effects of PM_(2.5) on the proliferation of VSMCs were evaluated by MTT method.The effects of different components of PM_(2.5) on inflammatory factors were determined by ELISA.The expression of MAPK proteins in VSMCs were detected by immunefluore scence assay.Results:The whole particles PM_(2.5)(WPPM_(2.5))and liposoluble-soluble,PM_(2.5)(LSPM_(2.5))inhibited the proliferation of VSMCs,and the IC_(50) values of 24 hours were 178.3 and 283.9μg/ml,respectively.LSPM_(2.5) could significantly enhance the expression of IL-8.U0126,SB2035850 and SP600125(MAPK signaling pathway inhibitors)could significantly inhibit the increase on IL-8,antagonize the inhibition of WPPM_(2.5) and LSPM_(2.5) on VSMCs,and increase the cell survival rate.WPPM_(2.5) and LSPM_(2.5) activated the phosphorylation of P38,JNK and ERK 1/2 signaling pathways in VSMCs,and increased the expression of phosphorylated proteins.Conclusion:PM_(2.5) inhibit VSMCs through MAPK inflammation signaling pathway,which is mainly related to its whole and liposoluble-soluble components.

关 键 词：细颗粒物 组分 血管平滑肌细胞 细胞毒性 炎性反应 丝裂原活化蛋白激酶信号通路 

分 类 号：R36[医药卫生—病理学]