Roles of leukotrienes in pathological states and therapentic application of 5-lipoxygenase inhibitors.

白三烯在病理状态中的作用和 5-脂氧合酶抑制剂的治疗应用。

• 批准号: 61480442
• 负责人: KATORI Makoto
• 金额: $ 3.78万
• 依托单位: Kitasato University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-61480442/
• 关键词: LTC_4; LTB_4; Simple purification method for LT; Rat cardiac infarction; Ethanol-induced gastric lesion; Microcirculation of hamster cheek pouch; 5ーリポキシゲナーゼ阻害薬; ラット遅延型アレルギー; 胸膜炎; LTB_4; 補体; 白血球血管外遊走; ロイコトリエンB_4; 5ーリポキシゲナーゼ; ラット遅延型アレルギー性胸膜炎 /

Roles of leukotrienes(LTs) in pathological states were analyzed in the following models: 1) Development of a simple purification method for RIA: Samples were acidified to PH 3.5 and LTs were separated by SEP-PAKC18. Recoveries of each LTs were more than 90%. 2) Tuberculin-induced rat pleurisy: Rats, sensitized by M.Tuberculosis H37 RA, were challenged by intrapleural injection of the same antigen. Plasma leakage showed three peaks at 3, 9-18, 48 hr and bradykinin and prostaglandins were involved, but LTs were not. Neither LTB4 nor complement was involved in neutrophils and mononuclear leukocyte migration in the exudate. 3) Rat cardiac infarction: ligation of left main coronary artery caused ischemia of 50% LV(left ventricle), which was reduced to 27% at 48 hr by reflow from surrounding tissue. Forty-two% of the LV became necrotic at 12 hr. Neutrophils were accumulated biphasically (up to 12 hr and 12-24 hr) in the cardiac tissue. LTB4, not LTC4, was generated in the cardiac tissue at a … More peak of 8 hr. A 5-lipoxygenase inhibitor (AA-861) attenuated the initial increase of neutrophils, whereas the second large increase was attributed to the complement component (C5a). The first increase of neutrophils played a pivotal role in enlargement of infarct size at 48 hr. 4) Ethanol-induced gastric lesion: Thirty of ethanol was placed in rat gastric lumen and this caused immediate cessation and congestion of blood in capillaries connected in the collecting venules. The LTC4 content in the stomach increased up to 4.4 ng/stomach (6 hold). LTC4 may constrict the collecting venules at the level of lamina muscularis. AA-861 attenuated the congestion of the stomach. 5) Microcirculation in hamster cheek pouch: Topical application of LTB4 over microvasculature caused rolling and adhesion o f neutrophils on the venular wall. More than 90% of the neutrophil adhered crossed the endothelial gap and stayed between endothelial cells and pericytes. They began to migrate to the interstitial space 30 min later. Less

通过以下模型分析了白三烯（LTs）在病理状态中的作用： 1）开发了一种简单的 RIA 纯化方法：将样品酸化至 PH 3.5，并通过 SEP-PAKC18 分离 LTs，每种 LTs 的回收率均大于 90。 % 2)结核菌素诱导的大鼠胸膜炎：由结核分枝杆菌H37 RA致敏的大鼠，通过胸腔内注射相同抗原进行攻击，血浆渗漏在 3、9-18、48 小时出现三个峰值，并且涉及缓激肽和前列腺素，但 LTB4 和补体均不涉及中性粒细胞和单核白细胞迁移。 3）大鼠心肌梗塞：结扎左冠状动脉导致左心室50%缺血。心室），48 小时时由于周围组织的回流而减少至 27%，12 小时时中性粒细胞在心脏组织中双相积累（最多 12 小时和 12-24 小时）。 LTB4，而不是 LTC4，是在 8 小时峰值时在心脏组织中产生的 5-脂氧合酶抑制剂。 (AA-861) 减弱了中性粒细胞的最初增加，而第二次大幅增加归因于补体成分 (C5a) 中性粒细胞的第一次增加在 48 小时时梗死面积的扩大中发挥了关键作用 4) 乙醇诱导。胃损伤：将30乙醇放入大鼠胃腔中，这导致与集合小静脉相连的毛细血管中的血液立即停止和充血。胃中的 LTC4 含量增加至 4.4 ng/胃（6 小时），LTC4 可能会收缩肌层水平的集合小静脉，从而减轻胃的充血。 5) 仓鼠颊囊中的微循环：局部应用。微脉管系统上的 LTB4 导致 90% 以上的中性粒细胞在小静脉壁上滚动和粘附。 30分钟后，中性粒细胞粘附穿过内皮间隙并停留在内皮细胞和周细胞之间。

项目成果

鹿取信、山本尚三、佐藤和雄、阿部圭志: "プロスタグランジンの最近の研究の進歩" 講談社サイエンティフィク, 443 (1987)

Makoto Katori、Shozo Yamamoto、Kazuo Sato、Keishi Abe：“前列腺素的最新研究进展”讲谈社科学，443（1987）

K. Sasaki; M. Katori; A. Ueno; S. Shigehiro; R. Kikawada: "A Role of leukotriene B_4 in exacerbration of myocardial infarction of the rat." Jpn. J. Inflammation. 6. 267-272 (1986)

K.佐佐木；

M.Katori,;Y.Harada,;A.Ueno,;M.Takahara,;T.Oda,;M.Kawamura,: Dermatologica.

M.Katori,;Y.Harada,;A.Ueno,;M.Takahara,;T.Oda,;M.Kawamura,：皮肤病学。

Kunio Tanaka: Prostaglandins. 31. 1099-1116 (1986)

田中邦夫：前列腺素。

K.Nagai;M.Katori: Int.J.Microcirc:Clin Exp. 7. 305-314 (1988)

K.Nagai；M.Katori：Int.J.Microcirc：Clin Exp。