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Studies on the inhibitory mechanism of MATS,a garlic oil component, to the thromboxane synthesis by platelets.

大蒜油成分MATS抑制血小板合成血栓素的机制研究

基本信息

批准号：
06660165
负责人：
ARIGA Toyohiko
金额：
$ 1.34万
依托单位：
Nihon University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

A potent platelet aggregation inhibitor, methyl allyl trisulfide (MATS) found in the steam distillled oil components from garlic (Allium sativum L.) was studied to reveal its inhibition mechanism. MATS suppressed synthesis of thromboxane A_2 (TXA_2) in platelets, and showed quite different mode of inhibition from the most of all known specific inhibitors, e.g., aspirin for cyclooxygenase (COX) , esculetin for lipoxygenase (LPX) and OKY-046 for thrombaxane synthase (TXS). MATS inhibited both COX and LPX,but TXS at the concentration lower 10^<-4>M.MATS was judged to inactivate prostaglandin endoperoxide synthase (PGH synthase) , however, the inhibition was confined to the direction toward one of its activities, peroxidase activity. COX activity the another activity of this bifunctional enzyme, which has been found to be inhibited specifically by aspirin, seemed to be unaffected by MATS,since arachidonic acid was consumed with the metabolic rate similar to the control. Although, the detailed interaction between MATS and PGH synthase is not demonstrated yet, MATS would prevent the reduction of a substrate (PGG_2) through its alkyl sulfides structure. Against PGI_2 generation by the endothelial cells of aortic vessel walls, MATS also affected to reduce its levels. These results made us suspicious whether MATS acts practically antithrombotic. Then, we are about to investigate in vivo effect of MATS using an animal model of thrombosis.

大蒜水蒸气蒸馏油成分中发现的一种有效的血小板聚集抑制物质--甲基烯丙基三硫化物(MATS)。对其缓蚀机理进行了研究。MATS抑制血栓素A_2(TXA_2)的合成，其抑制方式与大多数已知的特异性抑制剂如环氧合酶(COX)的阿司匹林、脂氧合酶(LPX)的秦皮乙素和血栓烷合成酶(TXS)的OKY-046截然不同。MATS对COX和LPX均有抑制作用，而TXS在10~(-4)和10~(-4)mg·L~(-1)时对前列腺素内源性过氧化物合成酶(PGH合酶)均有抑制作用，但抑制作用仅限于其活性之一的过氧化物酶活性。环氧合酶活性这种双功能酶的另一种活性被发现被阿司匹林特异性抑制，似乎不受MATS的影响，因为花生四烯酸的代谢速度与对照组相似。尽管MATS与PGH合成酶的详细相互作用尚不清楚，但MATS可通过其烷基硫化物结构阻止底物(PGG_2)的还原。MATS对主动脉内皮细胞产生的PGI_2也有抑制作用。这些结果使我们怀疑MATS是否具有实际的抗血栓作用。然后，我们将使用血栓形成的动物模型来研究MATS的体内效应。