Metz J, Wolf O, Schmelz A, Pill J, Stegmeier K H, Hartig F
Department of Anatomy and Cell Biology, University of Heidelberg, FRG.
Exp Pathol. 1991;41(2):57-69. doi: 10.1016/s0232-1513(11)80001-0.
These studies have examined aortic atherogenesis in cholesterol-fed rabbits and have correlated the effects of daltroban to the pathomechanism of the vessel wall lesions. After feeding a 0.5% cholesterol-enriched diet for 96 d atherosclerotic alterations were seen, which exhibited a proximo-distal pattern, to which the branching of the aorta contributed considerably. Depending on their localization and size a varying cellular constitution of the plaques was obvious. Large plaques, which were mainly seen in the aortic arch and the proximal descending thoracic aorta, consisted of numerous proliferating cells, masses of fibrillar ground substance, clusters of foam cells, and rarely contained cholesterol crystals and necroses. Emerging plaques mainly found in distal thoracic and abdominal aorta imposed as fatty streaks. Daltroban treatment, used in a clinically relevant doses of 10 mg/kg b. wt. per day, reduced extension and protrusional area of plaques to about 40%, which was evaluated using a newly developed computerized morphormetric method, in association with significant reductions in free cholesterol content within the aorta. The results suggest that daltroban inhibits the progression of atherosclerosis in cholesterol-fed rabbits. This effect may be related to its antagonistic interaction with the thromboxane A2 receptor and also to an inhibition of the cholesterol metabolism.
这些研究检测了用胆固醇喂养的兔子的主动脉粥样硬化形成情况，并将达曲班的作用与血管壁病变的发病机制联系起来。在喂食富含0.5%胆固醇的饮食96天后，可见动脉粥样硬化改变，呈现出近端至远端的模式，主动脉分支对此有很大影响。根据斑块的位置和大小，其细胞构成各不相同。主要见于主动脉弓和胸主动脉近端的大斑块由大量增殖细胞、纤维状基质团块、泡沫细胞簇组成，很少含有胆固醇结晶和坏死区域。主要见于胸主动脉远端和腹主动脉的新生斑块表现为脂纹。以临床相关剂量每天10mg/kg体重使用达曲班治疗，可使斑块的扩展和突出面积减少约40%，这是使用一种新开发的计算机形态测量方法评估得出的，同时主动脉内游离胆固醇含量也显著降低。结果表明，达曲班可抑制用胆固醇喂养的兔子的动脉粥样硬化进展。这种作用可能与其与血栓素A2受体的拮抗相互作用有关，也与胆固醇代谢的抑制有关。
