尼氟灭酸对支气管哮喘小鼠模型气道高反应性的抑制作用

目的　观察钙激活Cl-通道 (ClCa)阻断剂尼氟灭酸 (NFA)对支气管哮喘 (简称哮喘 )气道高反应性的抑制作用。方法　BALB/c小鼠 4 5只 ,按随机数字表法分为哮喘组 (A组 )、吸入NFA预防组 (B组 )和正常对照组 (C组 ) ,每组 15只。检测各组小鼠气道压力峰值 时间指数 (APTI)的差异 ,并比较各组小鼠支气管肺泡灌洗液 (BALF)中内皮素 1(ET 1)和一氧化氮 (NO)的含量。制备A组、C组小鼠的离体完整上皮气管环 (A1、C1组 )和去上皮气管环 (A2 、C2 组 ) ,观察在梯度浓度乙酰甲胆碱(mACh)的激发下 ,5 0 μmol/LNFA预处理对气管环收缩张力的影响。 结果　A组APTI与B组 (mACh为 2 .0mg/kg时 ,两者分别为 1.6 2± 0 .14和 1.2 1± 0 .0 7)比较 ,差异有显著性 (P <0 .0 1) ;A组BALF中ET 1和NO含量分别为 (10 3± 9)ng/L、(48.5± 3.2 ) μmol/L ,B组分别为 (5 3± 5 )ng/L和 (2 3.7± 2 .5 )μmol/L ,A组与B组比较差异有显著性(P <0 .0 1) ;离体气管环收缩张力实验显示 ,C1组完整上皮气管环的张力峰值比为 1.2 6± 0 .14 ,A1组完整上皮气管环的张力峰值比为 3.79± 0 .4 4 ,C2 组去上皮气管环的张力峰值比为 2 .0 6± 0 .18,A2 组去上皮气管环的张力峰值比为 2 .15± 0 .2 1,A1组与C1组、A1组与A2 组比较差异有显著性 (

The inhibiting effect of niflumic acid on airway hyperresponsiveness in asthmatic mice

OBJECTIVE: To evaluate the inhibiting effect of niflumic acid (NFA), an inhibitor of calcium-activated chloride channel (ClCa) on airway epithelium, on the airway hyperresponsiveness in asthmatic mice. METHODS: BALB/c mice were randomly divided into an asthma group (A group), a NFA prevention asthmatic group (B group) and a sham-challenged group (C group). The airway pressure time index (APTI) and the content of ET-1 and NO in bronchoalveolar lavage fluid (BALF) in all groups were measured. With the isolated tracheal rings with integral epithelium or epithelium removed from the asthma group (A(1) group and A(2) group) and the sham-challenged group (C(1) group and C(2) group), the contractile responsiveness of various rings to methacholine (mACh) was examined, and its change was observed when the rings were exposed to NFA beforehand. RESULTS: Compared with A group (1.62 +/- 0.14), the APTI in B group (1.21 +/- 0.07) was reduced remarkably (P < 0.01), and the contents of ET-1 (103 +/- 9) ng/L] and NO (48.5 +/- 3.2) micromol/L] in BALF of A group were significantly higher than those in B group, (53 +/- 5) ng/L, (23.7 +/- 2.5) micromol/L (P < 0.01), respectively]. The ratios of maximum contractility in A(1), A(2), C(1) and C(2) groups were (3.79 +/- 0.44), (2.15 +/- 0.21), (1.26 +/- 0.14) and (2.06 +/- 0.18), respectively. The contractility of A(1) group was highest among all groups (all P < 0.01), but could be effectively decreased by NFA. CONCLUSIONS: By inhibiting the special ClCa on the airway epithelium, NFA can inhibit the production of ET-1 and NO by epithelium and thus exert preventive effect on airway hyperresponsiveness in asthma.