Hirata Y, Umemura K, Nakano M, Uematsu T, Nakashima M
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Prostaglandins Leukot Essent Fatty Acids. 1994 Aug;51(2):81-6. doi: 10.1016/0952-3278(94)90082-5.
We have developed a photochemical model to induce thrombotic occlusion of the guinea-pig femoral artery. Using this model, we investigated the effect of cholesterol feeding on arterial occlusion time in the guinea-pig. Animals were divided into two groups, one on standard diet and the other on standard diet containing 0.5% cholesterol for 3 weeks. The time for femoral artery occlusion was significantly shorter (p < 0.05) in cholesterol fed animals as compared to the control group. In vitro collagen-, U-46619- (a thromboxane A2 adenosine diphosphate analogue) and (ADP)-induced platelet aggregation responses in whole blood in cholesterol-fed animals were increased 13-, 10- and 4-fold, respectively. U-46619- and collagen-induced washed platelet aggregation responses were also significantly enhanced by cholesterol feeding (p < 0.01). Further, TXA2 generation by collagen-stimulated washed platelets in cholesterol-fed animals increased similar to the platelet aggregation responses. However, platelet-activating factor (PAF)-induced platelet aggregation in whole blood was relatively unaffected by cholesterol feeding. 11-dehydro TXB2 levels in plasma were increased significantly by cholesterol feeding. Our observations suggest that increased plasma TXA2 level and platelet aggregation response to TXA2 and stimulated TXA2 synthesis in platelets play a role in enhanced arterial occlusion in cholesterol fed guinea-pigs.
我们建立了一种光化学模型来诱导豚鼠股动脉血栓形成闭塞。利用该模型，我们研究了喂食胆固醇对豚鼠动脉闭塞时间的影响。将动物分为两组，一组给予标准饮食，另一组给予含0.5%胆固醇的标准饮食，持续3周。与对照组相比，喂食胆固醇的动物股动脉闭塞时间显著缩短（p < 0.05）。喂食胆固醇的动物全血中，体外胶原蛋白、U - 46619（一种血栓素A2二磷酸腺苷类似物）和二磷酸腺苷（ADP）诱导的血小板聚集反应分别增加了13倍、10倍和4倍。喂食胆固醇也显著增强了U - 46619和胶原蛋白诱导的洗涤血小板聚集反应（p < 0.01）。此外，喂食胆固醇的动物中，胶原蛋白刺激的洗涤血小板产生血栓素A2的量与血小板聚集反应的增加相似。然而，血小板活化因子（PAF）诱导的全血血小板聚集相对不受喂食胆固醇的影响。喂食胆固醇显著提高了血浆中11 - 脱氢血栓素B2的水平。我们的观察结果表明，血浆血栓素A2水平升高、血小板对血栓素A2的聚集反应增加以及血小板中刺激的血栓素A2合成在喂食胆固醇的豚鼠动脉闭塞增强中起作用。
