钙激活Cl^-通道阻断剂对哮喘气道黏液高分泌的抑制研究  

Inhibition of airway mucus oversecretion in asthmatic mice by niflumic acid

作　　者：胡俊鸿[1] 宋立强[2] 段炜[1] 彭国华[1] 田耘[1] 

机构地区：[1]武警陕西总队医院内二科,西安710054 [2]第四军医大学西京医院呼吸科,西安710054

出　　处：《武警医学》2007年第4期253-256,F0003,共5页Medical Journal of the Chinese People's Armed Police Force

基　　金：武警部队后勤部科研项目(WKH2003033)

摘　　要：目的观察小鼠钙激活Cl-通道阻断剂尼氟灭酸(Niflumic acid,NFA)对哮喘小鼠气道黏液高分泌的抑制作用。方法将BABL/c小鼠随机分为哮喘组、吸入NFA预防组和正常对照组。AB-PAS特染法检测各组小鼠小支气管杯状细胞的数量及黏液分泌状况。RT-PCR法检测各组肺组织中黏蛋白MUC5AC mRNA和mClCA3 mRNA水平。结果正常对照组小支气管只有少量散在分布的杯状细胞,管腔干净;而哮喘组出现大量簇状分布的杯状细胞,胞质内富含着色颗粒,管腔具有着色黏液;NFA预防组的杯状细胞数量与正常对照组相近。哮喘组的MUC5AC及mClCA3 mRNA水平均显著高于正常对照组;NFA预防组的MUC5AC mRNA水平与正常对照组接近,而mClCA3 mRNA水平稍高于正常对照组。结论NFA能有效抑制哮喘小鼠气道杯状细胞数量的增加及黏蛋白的合成,这一效果是通过阻断mCLCA3活性和降低其表达水平来实现的。Objective To evaluate the inhibitory effect of niflumic aeid（NFA）, an inhibitor of murine calcium activated chloride channel of airway goblet cells, on airway mucus overproduction in asthmatic mice.Methods BABL/c mice were randomly divided into asthma group, NFA prevention asthmatic group, and normal control group. The cell count and the secretion of goblet cells in bronchioles of all groups were examined with AB- PAS staining. The levels of mucin MUCSAC mRNA and mCLCA3 mRNA were detected by reverse transcription polymerase chain reaction （RT- PCR） assay.Results Only a few goblet cells were scattered in the bronchioles of normal control group. But many aoblet cells filled with stained granules were found in asthma group, whereas NFA orevention group was similar to control group in number of goblet cells. Compared with normal group and NFA prevention group, asthmatic group had higher level of MUCSAC mRNA and mCLCA3 mRNA. NFA prevention group showed the same MUCSAC mRNA level as normal group, but higher mCLCA3 mRNA level.Conclusions NFA inhibits the increase in goblet cell and synthesis of mucus protein in asthmatic mice by inhibiting the activity and expression of mCLCA3.

关 键 词：哮喘 钙激活Cl^-通道阻断剂 杯状细胞 

分 类 号：R562.25[医药卫生—呼吸系统]