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

在以下模型中分析了白细胞（LTS）在病理状态中的作用：1）开发RIA的简单纯化方法：将样品酸性化至pH 3.5，LTS通过SEP-PAKC18分离。每个LT的回收率超过90％。 2）结核蛋白诱导的大鼠胸膜炎：大鼠，大麻菌血症H37 RA敏感，受到胸膜内注射相同抗原的挑战。等离子体泄漏显示3、9-18、48小时，Bradykinin和前列腺素的三个峰涉及，但LTS却没有。 LTB4和完成的嗜中性粒细胞和单核白细胞迁移均未涉及渗出液。 3）大鼠心脏梗塞：左主冠状动脉的连接导致缺血为50％LV（左心室），从周围组织中的反流在48小时时将其降低至27％。 42％的LV在12小时时变坏死。心脏组织中嗜中性粒细胞准确（长达12小时和12-24小时）。 LTB4而不是LTC4是在心脏组织中产生的，以……更多的8小时峰。 5-脂氧合酶抑制剂（AA-861）减弱了中性粒细胞的初始增加，而第二大增加归因于完成成分（C5A）。中性粒细胞的首次增加在48小时的梗塞大小增加中起着关键作用。 4）乙醇诱导的胃病变：将三十个乙醇放置在大鼠胃腔中，这导致收集静脉内有关的毛细血管中立即停止和血液充血。摊位中的LTC4含量增加到4.4 ng/胃（6固定）。 LTC4可能会在薄片肌中收集静脉。 AA-861衰减了摊位的拥塞。 5）仓鼠脸颊袋中的微循环：LTB4在微脉管系统上的局部应用导致静脉壁上的中性粒细胞滚动和广告。超过90％的中性粒细胞粘附在内皮间隙中，并在内皮细胞和周细胞之间停留。 30分钟后，它们开始迁移到间质空间。较少的

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。