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

白三烯（leukotrienes, LTs）在病理状态下的作用模型分析如下：1)建立一种简单的RIA纯化方法：将样品酸化至PH 3.5，用SEP-PAKC18分离LTs。各lt的回收率均在90%以上。2)结核菌素诱导的大鼠胸膜炎：用结核分枝杆菌H37 RA致敏的大鼠胸膜内注射相同的抗原。血浆渗漏在3、9 ~ 18、48小时出现3个峰值，与缓激肽和前列腺素有关，但与LTs无关。LTB4和补体均未参与渗出液中中性粒细胞和单核白细胞的迁移。3)大鼠心肌梗死：左冠状动脉主干结扎引起50%左心室缺血，48小时周围组织回流使左心室缺血减少至27%。42%的左室在12小时时坏死。中性粒细胞在心脏组织中双期积累（长达12小时和12-24小时）。LTB4，而不是LTC4，在心脏组织中产生的峰值为8小时。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小时梗死面积扩大中起关键作用。4)乙醇致胃病变：将30份乙醇置于大鼠胃腔内，引起集静脉连接的毛细血管立即停止和充血。胃中LTC4含量增加至4.4 ng/胃（6 hold）。LTC4可在肌层水平收缩集合小静脉。AA-861减轻了胃充血。5)仓鼠颊袋微循环：局部应用LTB4在微血管上引起小静脉壁上中性粒细胞滚动和粘附。90%以上的中性粒细胞粘附穿过内皮间隙，停留在内皮细胞和周细胞之间。30分钟后，它们开始向间隙区迁移。少

项目成果

佐々木幸二、鹿取信、上野晃憲、重広世紀子、木川田隆一: 炎症. 6. 267-272 (1986)

Koji Sasaki、Makoto Katori、Akinori Ueno、Chiko Shigehiro、Ryuichi Kikawada：炎症。 6. 267-272 (1986)

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

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

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。