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ELUCIDATION OF PATHOGENESIS OF ANAPHYLACTIC SHOCK AND DEVELOPMENT OF ITS SPECIFIC TREATMENT

过敏性休克发病机制的阐明及其特异性治疗的开发

基本信息

批准号：
09470336
负责人：
MITSUHATA Hiromasa
金额：
$ 7.81万
依托单位：
JUNTENDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 2000
项目状态：
已结题

项目摘要

1. The PARS inhibitor 3-aminobenzamide does not improve cardiac depression or bronchospasm provoked by systemic aggregated anaphylaxis in rabbits in vivo, implying that the pathophysiological changes associated with systemic anaphylaxis may not be related to activation of an energy-consuming DNA repair cycle trigged by PARS.These results, along with the lack of improvement in survival rates in PARS inhibitor-treated animals, imply that PARS may not play an important role in anaphylaxis, although direct proof of activation of PARS is lacking in this study.2. The administration of an inhibitor of PDEs 4 and 1, KF19514, either before or after antigen challenge, improved bronchoconstriction induced by systemic anaphylaxis in rabbits with minimal concomitant cardiovascular side effects compared with aminophylline, suggesting that PDE 4 inhibitors may be useful in the treatment of systemic anaphylaxis.3. The production of ET-1 rises rapidly during anaphylactic shock, suggesting that ET-1 may have a pathophysiological role during anaphylactic shock. The purpose of the present study was to investigate the role of ET-1 in the cardiovascular depression and bronchospasm provoked by anaphylaxis in vivo. In addition, to determine whether inhibition of ET-1 would improve cardiovascular and bronchospasm in anaphylaxis, we administered BQ610, an ETA receptor antagonist, to fentanyl anesthetized rabbits before the induction of anaphylaxis. In conclusion, ET-1 and ETA receptor does not play an important role in anaphylactic shock.4. Propfol is as effective as sevoflurane in attenuating bronchoconstriction associated with anaphylaxis in rabbits. Propofol may be a useful alternative to sevoflurane or isoflurane in the treatment of bronchospasm in asthma or anaphylaxis.

1. PARS抑制剂3-氨基苯甲酰胺不能改善兔体内全身性聚集性过敏反应引起的心脏抑制或支气管痉挛，这意味着与全身性过敏反应相关的病理生理变化可能与PARS触发的能量消耗DNA修复周期的激活无关。这些结果，以及PARS抑制剂治疗动物的存活率缺乏改善，意味着PARS可能在过敏反应中不起重要作用，尽管本研究缺乏PARS激活的直接证据。与氨茶碱相比，在抗原刺激前后给予pde4和1抑制剂KF19514，可改善家兔全身性过敏反应引起的支气管收缩，并伴有最小的心血管副作用，提示pde4抑制剂可用于全身性过敏的治疗。过敏性休克时ET-1的产生迅速升高，提示ET-1可能在过敏性休克中具有病理生理作用。本研究的目的是探讨ET-1在体内过敏性反应引起的心血管抑制和支气管痉挛中的作用。此外，为了确定抑制ET-1是否会改善过敏反应时的心血管和支气管痉挛，我们在过敏反应诱导前给芬太尼麻醉的家兔服用ETA受体拮抗剂BQ610。综上所述，ET-1和ETA受体在过敏性休克中并不起重要作用。异丙酚与七氟醚在减轻兔过敏反应相关的支气管收缩方面同样有效。异丙酚可能是一种有用的替代七氟醚或异氟醚在治疗支气管痉挛哮喘或过敏反应。