CAJ | 학술논문

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.
목적 관찰소서개격활록리자통도Ⅲ형(mCLCA3)조단제니불멸산(NFA)유도지기관효천(간칭효천)소서기도배상세포조망적작용.방법 장BABL/c소서수궤분위효천조、NFA치료조화정상대조조.소목정-이홍(HE)염색법검측각조소서폐조직만성염증상황,과전산-설부(PAS)특수염색법、면역조직화학법、말단전이매표기법(TUNEL)분별검측각조소서소지기관중배상세포적수량급점액분비상황、Bax단백표체、세포조망상황.결과 교정상대조조소서,효천조소서세지기관급혈관주위명현출현염증세포침윤,병유상피탈락,기도벽증후,NFA치료후상피세포탈락감소.교정상소서,효천조소서소지기관배상세포비례증다,점액분비증가(P＜0.05).NFA치료후,효천소서소지기관배상세포비례감소,점액고분비수억제,차배상세포표체Bax단백양성솔、세포조망솔증가(P＜0.05).배상세포표체Bax양성솔여세포조망솔정정상관(r=0.91,P＜0.01).결론 NFA가유효유도효천소서기도배상세포조망,기궤제가능시조단mCLCA3표체,개변배상세포내외생리배경,상조촉조망단백Bax표체,유도조망발생.
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 shamchallenged 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 mCLCA3 and up regulation activity and expression of Bax.