Gryglewski R J
CRC Crit Rev Biochem. 1980;7(4):291-338. doi: 10.3109/10409238009105464.
Metabolism of arachidonic acid (AA) in blood platelets and in vascular endothelium does not lead to prostaglandins, but thromboxane A2 and prostacyclin are generated. These labile metabolites of AA antagonize each other: thromboxane A2 is a vasoconstrictor and proaggregatory agent, whereas prostacyclin dilates arteries, prevents platelets from aggregation, and dissipates the preformed platelet clumps. Prostacyclin is a powerful stimulator of adenylate cyclase in platelets and therefore its antiplatelet action is potentiated by phosphodiesterase inhibitors such as theophylline or dipyridamole. Cyclo-oxygenase of AA is inhibited by aspirin, thromboxane synthetase by analogues of prostaglandin endoperoxides, and prostacyclin synthetase by linear lipid peroxides. A hypothesis is put forward that atherosclerosis develops because of pathological, nonenzymic lipid peroxides. A hypothesis is put forward that atherosclerosis develops because of pathological, nonenzymic lipid peroxydation in the body and the subsequent molecular damage to prostacyclin synthetase in the rheologically determined areas of arterial walls. Endothelium deprived of prostacyclin is the basis for microthrombi formation, and follows a sequence of events described by Rokitansky and later by Ross. Prostacyclin is also a circulating hormone which is generated by the lungs. Thereby a damage of this "endocrine gland" by respiratory disorders, air pollution, or tobacco smoking are likely to contribute to pathogenesis of atherosclerosis, myocardial infarction, and arterial thromboembolism. Pharmacological treatment and prevention of these diseases should logically include antioxydants, prostacyclin and its analogues, thromboxane synthetase inhibitors and perhaps cyclooxygenase inhibitors (aspirin ?). Prostacyclin was already infused intravenously to men and its powerful antiaggregatory and deaggregatory actions were demonstrated. These properties of prostacyclin along with its vasodilator and positive inotropic actions destine this hormone to be a new type of antithrombotic drug in acute myocardial infarction.
花生四烯酸（AA）在血小板和血管内皮中的代谢不会产生前列腺素，而是生成血栓素A2和前列环素。这些AA的不稳定代谢产物相互拮抗：血栓素A2是一种血管收缩剂和促聚集剂，而前列环素可扩张动脉、防止血小板聚集并消散预先形成的血小板凝块。前列环素是血小板中腺苷酸环化酶的强大刺激剂，因此其抗血小板作用会被磷酸二酯酶抑制剂（如茶碱或双嘧达莫）增强。AA的环氧化酶被阿司匹林抑制，血栓素合成酶被前列腺素内过氧化物类似物抑制，前列环素合成酶被线性脂质过氧化物抑制。有人提出一种假说，即动脉粥样硬化是由于病理性的非酶促脂质过氧化作用而发展的。还有一种假说认为，动脉粥样硬化是由于体内病理性的非酶促脂质过氧化以及随后在动脉壁流变学决定区域对前列环素合成酶的分子损伤而发展的。缺乏前列环素的内皮是微血栓形成的基础，其过程遵循罗基坦斯基以及后来罗斯所描述的一系列事件。前列环素也是一种由肺产生的循环激素。因此，呼吸系统疾病、空气污染或吸烟对这种“内分泌腺”的损害可能会促进动脉粥样硬化、心肌梗死和动脉血栓栓塞的发病机制。对这些疾病的药物治疗和预防在逻辑上应包括抗氧化剂、前列环素及其类似物、血栓素合成酶抑制剂，或许还包括环氧化酶抑制剂（阿司匹林？）。前列环素已经通过静脉注射给男性，并证明了其强大的抗聚集和解聚作用。前列环素的这些特性及其血管舒张和正性肌力作用注定这种激素将成为急性心肌梗死中一种新型的抗血栓药物。
