摘要
目的探讨VGX-1027能否抑制PM_(2.5)介导的小鼠肺部炎症和气道高反应。方法将成年健康C57BL/6小鼠随机分为对照组、VGX-1027(50 mg·kg^(-1))+PBS组、PM_(2.5)组、VGX-1027(12.5 mg·kg^(-1))+PM_(2.5)组、VGX-1027(25 mg·kg^(-1))+PM_(2.5)组和VGX-1027(50 mg·kg^(-1))+PM_(2.5)组。小鼠在鼻腔滴入PBS或PM_(2.5)混悬液(7.8 mg·kg^(-1))前1 h,腹腔注射PBS或相应剂量的VGX-1027,每天1次,连续2 d。24 h后,测定小鼠气道高反应,支气管肺泡灌洗液(BALF)细胞计数,HE染色评估肺部炎症积分,ELISA检测BALF炎性因子水平,Western blot测定肺组织NF-κB蛋白的磷酸化水平,以及NLRP3和caspase-1的表达水平。结果 PM_(2.5)鼻腔滴入引起明显的肺部炎症和气道高反应。12. 5 mg·kg^(-1)VGX-1027不能抑制PM_(2.5)介导的气道高反应和肺部炎症浸润;而25、50 mg·kg^(-1)的VGX-1027明显抑制PM_(2.5)介导的气道高反应和肺部炎症浸润,降低BALF中炎症细胞数量和炎性因子的水平;下调NF-κB蛋白的磷酸化水平,以及NLRP3和caspase-1的表达水平。结论VGX-1027可抑制PM_(2.5)介导的小鼠肺部炎症和气道高反应。
Aim To investigate whether VGX-1027 could prevent PM2.5 -induced mouse lung inflammation and airway hyperresponsiveness.Methods Forty-eight C57BL/6 mice were randomly divided into control group,VGX-1027(50 mg·kg^-1 )+PBS group,PM2.5 group,VGX-1027(12.5 mg·kg^-1 )+PM2.5 group,VGX-1027(25 mg·kg^-1 )+PM2.5 group,and VGX-1027(50 mg·kg^-1 )+PM2.5 group.Mice were injected intraperitoneally with PBS or corresponding doses of VGX-1027 one hour before intranasal instillation of PBS or PM2.5 (7.8 mg·kg^-1 ) for two consecutive days.24 hours after last intranasal instillation,airway hyperresponsiveness and bronchoalveolar lavage fluid (BALF) cell numbers were measured.Lung inflammation scores were evaluated by HE staining and the levels of inflammatory cytokines in BALF were detected by ELISA,and the expressed levels of NLRP3 and caspase-1,as well as the phosphorylation levels of NF-κB protein were determined using Western blotting.Results PM2.5 intranasal instillation induced significant lung inflammation and airway hyperresponsiveness.In the PM2.5 group,VGX-1027 at 12.5 mg·kg^-1 did not inhibit PM2.5 -induced airway hyperresponsiveness and lung inflammatory infiltration compared to PM2.5 -instilled mice;however,VGX-1027 at 25 and 50 mg·kg^-1 inhibited PM2.5 -induced airway hyperresponsiveness and lung inflammatory infiltration,decreased the number of inflammatory cells and the levels of inflammatory factors in BALF,and down-regulated NLRP3 and caspase-1 expression,as well as the phosphorylation levels of NF-κB.Conclusion VGX-1027 could inhibit PM2.5 -induced lung inflammation and airway hyperresponsiveness in mice.
作者
徐蒙蒙
韩晓燕
李锋
王沐昀
张海
陈宇清
张妍蓓
XU Meng-meng;HAN Xiao-yan;LI Feng;WANG Mu-yun;ZHANG Hai;CHEN Yu-qing;ZHANG Yan-bei(Cadre Respiratory and Critical Care,the First Affiliated Hospital of Anhui Medical University, Hefei 230022;Dept of Respiratory Medicine,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China;Dept of Pulmonary Medicine,Shanghai Chest Hospital,Shanghai Jiao Tong University of Medicine,Shanghai 200030,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2019年第4期545-550,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金重点国际(地区)合作研究项目(No 51420105010)
上海市科委"科技创新行动计划"实验动物研究领域项目(No 15140903400)
安徽高校自然科学研究项目(No KJ2018A0208)
