尼氟灭酸诱导支气管哮喘小鼠气道杯状细胞凋亡的研究  

Inductive effect of niflumic acid on the airway goblet cells apoptosis in asthmatic mice

作　　者：刘大鹏[1] 杨军兰[1] 任芳萍[1] 吴守振[1] 吴昌归[1] 宋立强[1] 

机构地区：[1]第四军医大学西京医院呼吸与危重症医学科,西安710032

出　　处：《中华哮喘杂志（电子版）》2013年第2期104-108,共5页Chinese Journal of Asthma(Electronic Version)

基　　金：国科金面上项目资助(81070029)

摘　　要：目的观察小鼠钙激活氯离子通道Ⅲ型(mCLCA3)阻断剂尼氟灭酸(NFA)诱导支气管哮喘(简称哮喘)小鼠气道杯状细胞凋亡的作用。方法将BABL/c小鼠随机分为哮喘组、NFA治疗组和正常对照组。苏木精-伊红(HE)染色法检测各组小鼠肺组织慢性炎症状况,过碘酸-雪夫(PAS)特殊染色法、免疫组织化学法、末端转移酶标记法(TUNEL)分别检测各组小鼠小支气管中杯状细胞的数量及黏液分泌状况、Bax蛋白表达、细胞凋亡状况。结果较正常对照组小鼠,哮喘组小鼠细支气管及血管周围明显出现炎症细胞浸润,并有上皮脱落,气道壁增厚,NFA治疗后上皮细胞脱落减少。较正常小鼠,哮喘组小鼠小支气管杯状细胞比例增多,黏液分泌增加(P<0.05)。NFA治疗后,哮喘小鼠小支气管杯状细胞比例减少,黏液高分泌受抑制,且杯状细胞表达Bax蛋白阳性率、细胞凋亡率增加(P<0.05)。杯状细胞表达Bax阳性率与细胞凋亡率呈正相关(r=0.91,P<0.01)。结论 NFA可有效诱导哮喘小鼠气道杯状细胞凋亡,其机制可能是阻断mCLCA3表达,改变杯状细胞内外生理环境,上调促凋亡蛋白Bax表达,诱导凋亡发生。Objective To evaluate the inductive effect of niflumic acid ( NFA ), an inhibitor of calcium-activated chloride channel ( CLCA ) on airway epithelium , on the airway goblet cells apoptosis in asthmatic mice.Methods BALB / c mice were randomly divided into an asthma group , a NFA treatment group and a sham-challenged asthmatic group.HE staining detected the chronic inflammation of the airway.PAS staining detected the cell counting and secretion of goblet cells.Immunohistochemistry method detected Bax proteins expression of goblet cells in small bronchus of all groups.TUNEL method detected apoptosis of goblet cells in small bronchus of all groups.Results Compared with sham-challenged asthmatic group , there was more significant inflammatory cell infiltration and epithelial shedding around the bronchus and perivascular of asthma group , and after NFA treatment the epithelial shedding is reduced.Compared with sham-challenged asthmatic group , there were more goblet cells and mucus secretion in the small bronchus of the asthma mice ( P <0.05 ), and the rate of goblet cells of small bronchus was reduced , and the mucus secretion was inhibited ( P <0.05 ), but the Bax protein expression positive rate and apoptosis rate of goblet cells of small bronchus was increased ( P <0.05 ) and positively correlated ( r =0.91 , P <0.01 ) .Conclusions NFA can induce the goblet cells apoptosis in asthmatic mice , through inhibition of activity and expression of mCLCA3and up regulation activity and expression of Bax.

关 键 词：尼氟灭酸 哮喘 杯状细胞 凋亡 

分 类 号：O65[理学—分析化学] R73[理学—化学]