Barnes P J
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
J Allergy Clin Immunol. 1993 Jul;92(1 Pt 2):197-9. doi: 10.1016/0091-6749(93)90107-q.
The recognition that asthma is a chronic inflammatory disease has focused attention on microvascular leakage, which is a component of the inflammatory process. Epithelial shedding, airway edema, increased airway resistance, and airway hyperresponsiveness can result from the plasma extravasation caused by leakage. The chain of inflammatory events set off by microvascular leakage may contribute to the development of the late-phase asthmatic response. Thus the search for drugs that ameliorate this leakage continues. Intravenous nedocromil sodium in a dose of 100 micrograms/kg is effective in blocking microvascular leakage induced by intravenous allergen in sensitized guinea pigs but has no effect on leakage induced by either intravenous histamine or platelet-activating factor, which suggests that it acts predominantly on mediator release. Studies in hamsters, however, have demonstrated that nedocromil sodium is effective in blocking leakage induced by histamine, which acts directly on endothelial cells. The ability of nedocromil sodium to reduce microvascular leakage may contribute to its effectiveness in preventing the late-phase response, but the mechanism by which this reduction occurs is not completely understood.
认识到哮喘是一种慢性炎症性疾病后，人们将注意力集中在微血管渗漏上，这是炎症过程的一个组成部分。上皮脱落、气道水肿、气道阻力增加和气道高反应性可能由渗漏引起的血浆外渗导致。微血管渗漏引发的一系列炎症事件可能促使迟发性哮喘反应的发生。因此，人们仍在寻找能改善这种渗漏的药物。剂量为100微克/千克的静脉注射奈多罗米钠可有效阻断致敏豚鼠静脉注射变应原诱导的微血管渗漏，但对静脉注射组胺或血小板活化因子诱导的渗漏无效，这表明它主要作用于介质释放。然而，对仓鼠的研究表明，奈多罗米钠可有效阻断组胺诱导的渗漏，组胺直接作用于内皮细胞。奈多罗米钠减少微血管渗漏的能力可能有助于其预防迟发性反应的有效性，但其发生这种减少的机制尚不完全清楚。
