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

用以下模型分析了白三烯(LTS)在病理状态中的作用：1)建立了一种简单的RIA纯化方法：样品酸化至PH3.5，LTS经SEP-PAKC18分离。加样回收率均在90%以上。2)结核菌素致大鼠胸膜炎：用结核分枝杆菌H37 RA致敏大鼠，胸膜腔内注射相同抗原。血浆渗漏在3、9~18、48h出现3个高峰，涉及缓激肽和前列腺素，而LTS未见异常。渗出液中的中性粒细胞和单核白细胞迁移与LTB4和补体无关。3)大鼠心肌梗死：结扎左冠状动脉主干造成50%的左心室(LV)缺血，48小时后从周围组织回流使其减少到27%。12小时后，42%的左心室开始坏死。中性粒细胞在心脏组织中呈双相性聚集(长达12小时和12-24小时)。LTb4，而不是LTC4，是在…时在心脏组织中产生的更多的高峰期为8小时。5-脂氧合酶抑制剂(AA-861)减弱了最初中性粒细胞的增加，而第二大增加归因于补体成分(C5a)。中性粒细胞首次增多在48小时后梗塞面积扩大中起关键作用。4)乙醇致大鼠胃损伤：30只大鼠胃腔内放置30%乙醇，可引起集合微静脉连接的毛细血管立即停血充血。胃中的LTC4含量增加到4.4 ng/胃(6个持续期)。LTC4可在肌层水平收缩集合小静脉。AA-861可减轻胃充血。5)金黄地鼠颊囊微循环：局部应用LTB4覆盖微血管，导致中性粒细胞在静脉壁上滚动和粘连。90%以上的中性粒细胞黏附穿过内皮细胞间隙，停留在内皮细胞和周细胞之间。30分钟后，它们开始向间隙迁移。较少

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