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  

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

作　　者：宋立强[1] 李妍[2] 张乐宁[3] 高放[3] 程九华[3] 戚好文[1] 

机构地区：[1]第四军医大学西京医院呼吸内科,西安710033 [2]第四军医大学西京医院心脏内科,西安710033 [3]第四军医大学航空生理教研室,西安710033

出　　处：《中华结核和呼吸杂志》2004年第2期108-111,共4页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：2 0 0 3年西安市社会发展计划项目 (SF2 0 0 3 3 7)

摘　　要：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 (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) μmol/L] in BALF of A group were significantly higher than those in B group, [(53±5) ng/L,(23.7±2.5) μmol/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.

关 键 词：尼氟灭酸 支气管哮喘 小鼠模型 气道高反应性 抑制作用 

分 类 号：R965[医药卫生—药理学]