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吸入肝素对支气管哮喘患儿白三烯后支气管收缩的影响

[The effect of inhaled heparin on post-leukotriene bronchoconstriction in children with bronchial asthma].

作者信息

Stelmach Iwona, Jerzyńska Joanna, Bobrowska Monika, Brzozowska Agnieszka, Majak Paweł, Kuna Piotr

机构信息

Samodzielny Oddział Kliniczny Interny Dzieciecej i Alergologii Instytutu Pediatrii Akademii Medycznej w Łodzi.

出版信息

Pol Merkur Lekarski. 2002 Feb;12(68):95-8.

Abstract

Heparin besides its anticoagulant properties, possesses anti-inflammatory actions. Inhaled heparin has been shown to reduce early and late phase of asthmatic reaction and suppresses allergen induced rise in bronchial hyperreactivity. The exact mechanism of heparin action in bronchial asthma remains obscure. The mechanism involved in the control of bronchial hyperreactivity by heparin has been studied little and is yet poorly understood. The purpose of the present study was to investigate the effect of inhaled heparin on the airway response to leukotriene D4 Fourteen children with typical history of mild atopic asthma participated in this randomized, double-blind, placebo controlled and cross-over study. At the first visit subjects underwent provocation challenge test with leukotriene D4. Patients came back 14 days later to inhale heparin or placebo followed by provocation test with leukotriene. The third study day was 14 days after the second day and provocation test was performed in the same manner except for that patients who inhaled heparin at the second visit, now were administered placebo and opposite. Ten patients completed the study. One patient was withdrawn from the study because of consent withdrawal and three patients were unable to complete the provocation test because of asthma exacerbation. Single dose of inhaled heparin significantly decreased bronchial hyperreactivity to leukotriene in children with mild asthma (p = 0.005). PC20L after heparin inhalation increased in eight patient and decreased in two. It has been shown that histamine, metacholine, and leukotriene play a role in eosinophil recruitment to the airway. Since histamine, metacholine and leukotriene act through receptor binding to protein G, it is possible that heparin (by displacing eosinophil proteins from receptor-protein G binding) restore binding between receptor and G protein and in such mechanism, decrease bronchial hyperreactivity to leukotriene. In our study heparin was inhaled just before leukotriene provocation test and thus the effect of heparin on eosinophil proteins is less likely possible.

摘要

肝素除了具有抗凝特性外,还具有抗炎作用。吸入肝素已被证明可减轻哮喘反应的早期和晚期阶段,并抑制变应原诱导的支气管高反应性升高。肝素在支气管哮喘中的确切作用机制仍不清楚。肝素控制支气管高反应性的机制研究较少,目前仍知之甚少。本研究的目的是探讨吸入肝素对气道对白三烯D4反应的影响。14名有典型轻度特应性哮喘病史的儿童参与了这项随机、双盲、安慰剂对照和交叉研究。在第一次就诊时,受试者接受了白三烯D4激发试验。患者在14天后回来吸入肝素或安慰剂,然后进行白三烯激发试验。第三个研究日是在第二天之后的14天,除了在第二次就诊时吸入肝素的患者现在给予安慰剂,而之前给予安慰剂的患者现在给予肝素外,激发试验以相同方式进行。10名患者完成了研究。1名患者因撤回同意书退出研究,3名患者因哮喘加重无法完成激发试验。单剂量吸入肝素显著降低了轻度哮喘儿童对白三烯的支气管高反应性(p = 0.005)。吸入肝素后,8名患者的PC20L升高,2名患者降低。已经表明,组胺、乙酰甲胆碱和白三烯在嗜酸性粒细胞向气道募集过程中起作用。由于组胺、乙酰甲胆碱和白三烯通过与G蛋白结合的受体起作用,肝素(通过从受体 - G蛋白结合中置换嗜酸性粒细胞蛋白)有可能恢复受体与G蛋白之间的结合,并通过这种机制降低支气管对白三烯的高反应性。在我们的研究中,肝素是在白三烯激发试验前立即吸入的,因此肝素对嗜酸性粒细胞蛋白的影响可能性较小。

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