噻托溴铵调控MAPK/NF-κB信号通路对气道平滑肌细胞增殖的影响及机制研究  

Tiotropium Bromide Affects Airway Smooth Muscle Cell Proliferation through Regulating MAPK/NF-κB Signaling Pathway

作　　者：李妮 张静 LI Ni;ZHANG Jing(Department of Pharmacy,Central Hospital of Tongchuan Mining Bureau,Tongchuan 727000,China;Department of Pharmacy,the 986 th Hospital of the Air Force,Xi’an 710054,China)

机构地区：[1]铜川矿务局中心医院药剂科,陕西铜川727000 [2]空军第九八六医院药剂科,西安710054

出　　处：《南昌大学学报（医学版）》2024年第1期14-19,24,共7页Journal of Nanchang University：Medical Sciences

基　　金：陕西省医学科学研究课题计划(2019JM3334)。

摘　　要：目的探究噻托溴铵通过MAPK/NF-κB信号通路对哮喘的影响及其潜在的机制。方法用10 ng·mL^(-1)血小板衍生生长因子(platelet-derived growth factor,PDGF)-BB和不同浓度(0、5、10、20、50μmol·L^(-1))噻托溴铵处理气道平滑肌细胞(airway smooth muscle cells,ASMCs),并通过CCK-8实验、克隆形成实验、划痕愈合实验和Transwell法分析ASMCs细胞增殖、迁移和侵袭;Western blot分析MMP2、MMP9、calponin和α-SMA的蛋白水平;Western blot检测MAPK/NF-κB信号通路的水平。结果噻托溴铵抑制PDGF-BB诱导的ASMCs的增殖、迁移和侵袭(P<0.05)。噻托溴铵调节ASMCs的表型转变(P<0.05)。噻托溴铵可以抑制PDGF-BB诱导的MAPK/NF-κB信号通路激活,降低p-38、p-JNK、p-ERK、p-p65、p-NF-κB的表达(P<0.05)。结论噻托溴铵可以通过阻断MAPK/NF-κB信号转导抑制ASMCs的增殖和迁移。推测噻托溴铵可以作为一种治疗哮喘的有前途的药物。Objective To investigate the effect of tiotropium bromide on asthma through the MAPK/NF-κB signaling pathway and its potential mechanism.Methods Airway smooth muscle cells(ASMCs)were treated with 10 ng·mL^(-1) platelet-derived growth factor-BB(PDGF-BB)and different concentrations oftiotropium bromide(0,5,10,20 and 50μmol·L^(-1)).The proliferation,colony formation ability,migration and invasion of ASMCs were analyzed by CCK-8,colonyformation,scratch wound healing and Transwell assays,respectively.The expression levels of MMP2,MMP9,calponin,α-SMAand MAPK/NF-κB signaling pathway proteins were analyzed by Western blot.Results Tiotropium bromide inhibited PDGF-BB-induced proliferation,migration and invasion and modulated phenotypic transformation in ASMCs(P<0.05).Furthermore,tiotropium bromide inhibited DGF-BB-caused activation of MAPK/NF-κB signaling pathway,and reduced the expression of p-38,p-JNK,p-ERK,p-p65 and p-NF-κB(P<0.05).Conclusion Tiotropium bromide can inhibit the proliferation and migration of ASMCs by blocking MAPK/NF-κB signal transduction.It is speculated that tiotropium bromide can be used as a promising drug for the treatment of asthma.

关 键 词：噻托溴铵 MAPK/NF-κB信号通路 气道平滑肌细胞 增殖 哮喘 

分 类 号：R915[医药卫生—微生物与生化药学]