尼氟灭酸对急性低氧人肺动脉收缩的影响  

Effects of niflumic acid on the pulmonary vasoconstriction of human in acute hypoxia conditions

作　　者：杨朝[1] 耑冰[1] 张丽萍[1] 张珍祥[2] 

机构地区：[1]宁夏自治区人民医院呼吸内科,宁夏银川750021 [2]华中科技大学同济医学院附属同济医院呼吸病研究所,湖北武汉430030

出　　处：《中国药理学通报》2011年第3期428-431,共4页Chinese Pharmacological Bulletin

基　　金：宁夏自然科学基金资助项目(NoNZ09146)

摘　　要：目的研究钙激活氯离子(ClCa)通道阻滞剂尼氟灭酸(NFA)对急性低氧人肺动脉收缩的影响。方法在常氧(37℃、5%CO2、21%O2、74%N2)和急性低氧(37℃、5%CO2、2%O2、93%N2)条件下,采用荧光分光光度计法、离体血管灌流法,观察ClCa阻滞剂NFA和indaryloxyacetic acid(IAA-94)对急性低氧人肺动脉平滑肌细胞质内游离钙离子浓度([Ca2+]i)及肺动脉张力的影响。结果①急性低氧引起[Ca2+]i升高,由常氧时的(103.26±4.72)nmol.L-1升高至(253.89±9.82)nmol.L-1(P<0.01);加入NFA、IAA-94使[Ca2+]i明显下降,最低至(107.18±14.99)nmol.L-1(P<0.01);②急性低氧引起肺动脉环收缩,由常氧时的(4.54±0.52)g.g-1至最大收缩张力(49.51±1.30)g.g-1(P<0.01);加入NFA和IAA-94后,它们均能抑制由低氧引起的血管收缩,使收缩张力最低降至(4.50±0.40)g.g-1(P<0.01)。结论 NFA能有效抑制急性低氧引起的肺动脉收缩,这一效果可能是通过抑制ClCa通道活性来实现的。Aim To investigate the effects of nifiumic acid（NFA）,an inhibitor of calcium-activated chloride（ClCa）channels,on pulmonary vasoconstriction of human in acute hypoxic conditions.Methods Acute hypoxia-induced contraction was observed in human pulmonary artery by using routine blood vascular perfusion in vitro;the fluorescence Ca2＋ indicator Fura-2/AM was used to observe intracellular free Ca2＋ concentration（i） in human pulmonary artery smooth muscle cells（PASMCs）through putting into ClCa channel blockers NFA and indaryloxyacetic acid（IAA-94）in normal（37℃,5% CO2,21% O2,74% N2）and acute hypoxic（37℃,5% CO2,2% O2,93% N2）conditions.Results ① In acute hypoxic condition,i was increased：in normoxic condition,i was（103.26±4.72）nmol·L-1,and in hypoxic condition,i was（253.89±9.82）nmol·L-1（P0.01）;The NFA and IAA-94 decreasedi from（253.89±9.82）nmol·L-1 to（107.18±14.99）nmol·L-1（P0.01）.② Acute hypoxia evoked pulmonary artery contractions from（4.54±0.52）g·g-1 to（49.51±1.30）g·g-1（P0.01）;The NFA and IAA-94 inhibited hypoxia-evoked contractions in the pulmonary artery from（49.51±1.30）g·g-1 to（4.50±0.40）g·g-1（P0.01）.Conclusions NFA can inhibit the contraction of human pulmonary artery in acute hypoxic condition,which may result from the inhibition of activity ClCa channels.

关 键 词：尼氟灭酸 钙激活氯离子通道 血管张力 低氧 肺动脉平滑肌 细胞质内游离钙离子浓度 

分 类 号：R322.121[医药卫生—人体解剖和组织胚胎学] R322.74[医药卫生—基础医学]