p38MAPK抑制剂对激素抵抗型哮喘患者肺泡巨噬细胞炎性因子的作用  

Effect of p38 MAPK inhibitor on inflammatory cytokines from alveolar macrophages of patients with steroid-resistant asthma

作　　者：梁丽 马佳韵 申海霁 施宇衡 李尧 张杰[1] 陈艳艳 陈振和 LIANG Li;MA Jia-yun;SHEN Hai-ji;SHI Yu-heng;LI Yao;ZHANG Jie;CHEN Yan-yan;CHEN Zhen-he(Department of Respiratory Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201999, China)

机构地区：[1]上海交通大学医学院附属第九人民医院呼吸科,上海201999

出　　处：《临床肺科杂志》2019年第1期22-26,共5页Journal of Clinical Pulmonary Medicine

基　　金：上海市卫生局科研项目(No 20134087);国家自然科学青年基金项目(NO.81670316)

摘　　要：目的探讨p38 MAPK抑制剂SB239063对激素抵抗型哮喘患者肺泡巨噬细胞炎性因子的作用。方法选取急性发作的哮喘患者,分为激素抵抗型哮喘组(简称SR组)与激素敏感性哮喘组(简称SS组)。采用ELISA及RT-qPCR方法检测肺泡灌洗液中巨噬细胞的CCL11,IL-8及IL-13蛋白和mRNA水平。分析比较单独地塞米松刺激或联合SB239063及地塞米松刺激,对不同组肺泡灌洗液中巨噬细胞的CCL11、IL-8及IL-13水平的影响。结果经脂多糖诱导后,与SS组相比,SR组患者肺泡灌洗液中巨噬细胞CCL11、IL-8及IL-13水平增高,差异具有统计学意义(P <0. 05)。采用地塞米松处理后,SS组肺泡灌洗液中巨噬细胞的CCL11、IL-8及IL-13水平下调,差异具有统计学意义(P <0. 05),而SR组肺泡灌洗液中巨噬细胞CCL11、IL-8及IL-13水平与处理前相比无明显变化,其差异无统计学意义(P> 0. 05)。联合SB239063及地塞米松处理后,SR组CCL11、IL-8、IL-13水平下调,差异有统计学意义(P <0. 05)。结论 p38 MAPK抑制剂可降低SR哮喘患者的肺泡巨噬细胞炎性因子的表达,提高激素治疗的敏感性,为SR哮喘治疗提出新思路。Objective To explore the effect of p38 MAPK inhibitor SB239063 on the secretion of inflammatory cytokines from alveolar macrophages(AMs)of patients with steroid-resistant asthma.Methods Patients with acute exacerbation of asthma were divided into the steroid-resistant asthma group(the SR group)and the steroid-sensitive asthma group(the SS group).The protein and mRNA levels of CCL11,IL-8 and IL-13 from AMs were detected by ELISA and RT-qPCR.The effects of single dexamethasone or combination of SB239063 and dexamethasone on the levels of CCL11,IL-8 and IL-13 from AMs of different groups were compared.Results Compared with the SS group,the levels of CCL11,IL-8 and IL-13 from AMs in SR patients were significantly higher than those of the SS group after being induced by lipopolysaccharide(P<0.05).Dexamethasone treatment could reduce the levels of CCL11,IL-8 and IL-13 effectively in AMs of the SS group(P<0.05),while it had no inhibitory effect in the SR group.The levels of CCL11,IL-8 and IL-13 in the SR group were down-regulated by the combination of SB239063 and dexamethasone(P<0.05).Conclusion p38 MAPK inhibitor could reduce the expression of inflammatory cytokines in AMs of SR and improve the sensitivity of hormone therapy,which suggests a new idea for the treatment of SR asthma.

关 键 词：激素抵抗型哮喘 肺泡巨噬细胞 p38MAPK SB239063 炎性因子 

分 类 号：R562.25[医药卫生—呼吸系统]