Characterisation of guinea pig precision-cut lung slices:: comparison with human tissues
Characterisation of guinea pig precision-cut lung slices:: comparison with human tissues
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DOI：
10.1183/09031936.06.00004206
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发表时间：
2006-09-01
影响因子：
24.3
通讯作者：
Martin, C.
中科院分区：
文献类型：
--
作者：
Ressmeyer, A. R.;Larsson, A. K.;Martin, C.
精密切割肺切片(PCL)可以比较不同物种在相同实验条件下的呼吸道反应。本研究的目的是建立和鉴定豚鼠(GP)的PCLS，并将其与人PCLS进行比较。GP PCLS的制备方法按以前发表的程序进行，只是琼脂糖液和初始孵育液中含有异丙肾上腺素，以避免死后呼吸道收缩。激动剂对GP和PCLS引起的支气管收缩的半数有效浓度(EC50)分别为：白三烯D-4(1.8，5.0)；血栓烷(16，1.3)；5-羟色胺(69，无反应)；组胺(217，2,170)；和乙酰甲胆碱(231,234)。组胺或血栓素-前列腺素受体拮抗剂可减弱变应原诱导的被动增敏PCLS的支气管收缩作用，与白三烯受体拮抗剂联用几乎可完全阻止。预先与乙酰甲胆碱收缩的气道被β-促性剂沙丁胺醇或磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤所松弛。对呼吸道和血管的同时研究是可能的，例如，内皮素-1的EC50值为37 NM(肺动脉)、10 NM(肺静脉)和9.6 NM(气道)。与先前在大鼠和小鼠身上的发现相比，这些数据表明豚鼠肺比大鼠或小鼠的肺更适合用于人类呼吸道药理学的模型。
Precision-cut lung slices (PCLS) allow comparison of the airway responses of different species under identical experimental conditions. The aim of this study was to establish and characterise PCLS from guinea pigs (GPs) and to compare them with human PCLS.GP PCLS were prepared according to previously published procedures with the exception that the agarose solution and the initial incubation medium contained isoproterenol to avoid post mortern airway contraction. The median effective concentrations (EC50, expressed as nM) for agonist-induced bronchoconstriction in GP and human PCLS, respectively, were: leukotriene D-4 (1.8, 5.0); thromboxane (16, 1.3); serotonin (69, unresponsive); histamine (217, 2,170); and methacholine (231, 234). Allergen-induced bronchoconstriction of passively sensitised PCLS was attenuated by histamine or thromboxane-prostanold receptor antagonists and was almost completely prevented by their combination with leukotriene receptor antagonists. Airways pre-contracted with methacholine were relaxed by the beta-gonist salbutamol or the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Simultaneous studies of airways and vessels are possible with, for example, EC50 values for endothelin-1 of 37 nM (pulmonary arteries), 10 nM (pulmonary veins) and 9.6 nM (airway).When compared with previous findings in rat and mouse, these data show that guinea pig lungs are a more appropriate model for human airway pharmacology than lungs from rats or mice.