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

• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-09470336/
• 关键词: ANAPHYLAXIS; 3-AMINOBENZAMIDE; PHOPHODIESTERASE 4 AND 1; ENDOTHELIN; PROPFOL; SEVOFLURANE; SHOCK; アナフィラキシー; 気管支けいれん; プロポフォール; セボフルレン; ショック; エンドセリン; 病態; phosphodiesterase inhibitor; アナフィラキシ-; PARS; 一酸化窒素

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家兔体内由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触发的耗能DNA修复周期的激活无关。这些结果以及PARS的存活率缺乏改善 抑制剂治疗的动物，表明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。2．与氨茶碱相比，在抗原攻击之前或之后给予 PDE 4 和 1 抑制剂 KF19514，可改善兔子由全身过敏反应引起的支气管收缩，同时伴随的心血管副作用最小，表明 PDE 4 抑制剂可能可用于治疗全身过敏反应。 3。过敏性休克期间 ET-1 的产生迅速增加，表明 ET-1 可能在过敏性休克期间具有病理生理作用。本研究的目的是探讨 ET-1 在体内过敏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中的心血管和支气管痉挛，我们在诱导过敏反应之前给芬太尼麻醉的兔子施用 BQ610（一种 ETA 受体拮抗剂）。综上所述，ET-1和ETA受体在过敏性休克中并不起重要作用。 4．异丙酚在减轻兔子过敏反应相关的支气管收缩方面与七氟醚一样有效。丙泊酚可能是七氟烷或异氟烷治疗哮喘或过敏反应中支气管痉挛的有用替代品。

项目成果

Hasome, N.: "An isoenzyme-selective inhibitor of phosphodiesterase 4 and 1. KF19514, may be useful in the treatment of systemic anaphylaxis an in vivo study in rabbits."Shock. 12. 46-53 (1999)

Hasome, N.：“磷酸二酯酶 4 和 1 的同工酶选择性抑制剂。KF19514，可能有助于治疗兔子的全身过敏反应。”休克。

Hasome, N.: "An isoenzyme-selective inhibitor of phosphodiesterase 4 and 1, KF19514, may be useful in the treatment of systemic anaphylaxis : an in vivo study in rabbits"Shock. 12-1. 46-53 (1999)

Hasome, N.：“磷酸二酯酶 4 和 1 的同工酶选择性抑制剂 KF19514，可能可用于治疗全身性过敏反应：兔子体内研究”休克。

Takeuchi H, Mitsuhata H,et al.: "An inhibitor of poly (adenosine 5'-diphosphoribose) synthetase,3-aminobenzamide,does not improve cardiovascular depression,bronchospasm,or survival associated with systemic anaphylaxis in rabitts in vivo." Shock. 8・2. 147-

Takeuchi H、Mitsuhata H 等人：“聚（腺苷 5-二磷酸核糖）合成酶抑制剂 3-氨基苯甲酰胺不会改善兔子体内心血管抑制、支气管痉挛或与全身性过敏反应相关的存活率。”休克。 8・2.147-

Takeuchi H: "An inhibitor of poly(adenosine 5-diphosphoribose)synthetase 3-aminobenzamide, does not improve cardiovascular depression, bronchospasm, or survival associated with systemic anaphylaxis in rabbits in vivo."Shock. 8. 147-152 (1997)

Takeuchi H：“聚（腺苷 5-二磷酸核糖）合成酶 3-氨基苯甲酰胺的抑制剂，不会改善兔子体内心血管抑制、支气管痉挛或与全身性过敏反应相关的生存。”休克。

Takeuchi, H.: "An inhibitor of poly(adenosine 5'-diphosphoribose)synthetase, 3-aminobenzamide, does not improve cardiovascular depression, bronchospasm, or survival associated with systemic anaphylaxis in rabbits in vivo."Shock. 8-2. 147-52 (1997)

Takeuchi, H.：“聚（腺苷 5-二磷酸核糖）合成酶抑制剂 3-氨基苯甲酰胺，不会改善兔子体内心血管抑制、支气管痉挛或与全身性过敏反应相关的生存。”休克。