半胱氨酰白三烯受体拮抗剂对气道结构细胞内皮素1表达的影响  

Zafirlukast inhibition of leukotriene C_(4) induced endothelin-1 expression in human airway structural Cell

作　　者：陈爱欢[1] 钟南山[1] 

机构地区：[1]广州呼吸疾病研究所,510120

出　　处：《中华结核和呼吸杂志》2000年第10期617-620,共4页Chinese Journal of Tuberculosis and Respiratory Diseases

摘　　要：目的　探讨半胱氨酰白三烯 (CysLTs)受体拮抗剂 (扎鲁司特 )对白三烯C4 (LTC4 )刺激人气道结构细胞内皮素 1(ET 1)基因表达及分泌的影响。方法　在离体培养人气道上皮细胞株 (16 HBE)和气道平滑肌细胞 (ASMC)培养液中加入扎鲁司特 ,采用酶联免疫吸附 (ELISA)法检测培养液ET 1水平 ;用逆转录多聚酶链反应 (RT PCR)方法检测ET 1mRNA表达量。结果　扎鲁司特可抑制LTC4 诱导 16 HBE及ASMCET 1mRNA表达及ET 1释放。 16 HBEET 1mRNA由 0 2 3± 0 10降至 0 10± 0 0 3,ET 1由 (12 7± 1 3)ng/L降至 (5 5± 2 6 )ng/L ,前、后比较差异有显著性 (t分别为 3 6 98和4 6 93,P分别为 0 0 34和 0 0 19) ;ASMCET 1mRNA由 0 13± 0 0 4降至 0 0 4± 0 0 2 ;ET 1由 (7 5± 1 0 )ng/L降至 (4 4± 0 9)ng/L ,前、后比较差异有显著性 (t分别为 4 6 2 9和 5 0 0 3,P分别为 0 0 19和0 0 0 7)。结论　扎鲁司特能抑制LTC4 诱导 16 HBE及ASMCET 1mRNA表达及ET 1释放 ,这可能是CysLTs受体拮抗剂抗气道炎症的机制之一。Objective To investigate the effects of a cysteinyl leukotriene receptor antagonist (zafirlukast) on endothelin 1(ET 1) expression in human airway epithelial cell line (16 HBE) and airway smooth muscle cells (ASMC) in response to leukotriene C 4 (LTC 4) stimulation. Methods 16 HBE or ASMC was incubated with 10 8 mol/L LTC 4 and graded concentrations of zafirlukast ET 1 level in supernatant was determined by ELISA and ET 1 mRNA expression was assessed by RT PCR. Results (1) LTC 4 induced ET 1 mRNA expression in 16 HBE and ASMC was significantly inhibited by zafirlukast (10 8 mol/L ) 0 23±0 10 vs 0 10±0 03 (16 HBE), t =3 698, P =0 034; 0 13±0 04 vs 0 04±0 02 ASMC, t =4 629, P =0 019 (2) When graded concentrations of zafirlukast (0, 10 12 mol/L, 10 10 mol/L, 10 8 mol/L, 10 6 mol/L ) were added to the LTC 4 cultured 16 HBE and ASMC, a significant inhibition of ET 1 production was observed in both groups cultured with 10 8 mol/L or more zafirlukast [(12 7±1 3) ng/L vs (5 5±2 6) ng/L 16 HBE, t =4 693, P =0 019; (7 5±1 0) ng/L vs (4 4±0 9) ng/L ASMC ( t =5 003, P =0 007)] (3) There was a significant negative linear correlation between ET 1 levels and zafirlukast concentrations in LTC 4 treated 16 HBE and ASMC (16 HBE: r =-0 9177, P =0 0289; ASMC: r =-0 9451, P =0 0153). Conclusions These data suggest that zafirlukast inhibis LTC 4 induced ET 1 over expression 16 HBE and ASMC, which may be one of the anti inflammatory mechanism of LTs receptor antagonists Key word Leukotriene receptor antagonist; Airway epithelial cell; Airway smooth muscle cell; Endothelin1) The serum GAS concentrations in patient group were much higher than those in control group ( F =13.003, P <0.01); ther

关 键 词：白三烯受体拮抗剂 气道上皮细胞结构 气道平滑肌细胞 内皮素 

分 类 号：R974.3[医药卫生—药品]