Workman J R, Schmidt S P, Donovan D L, Clarke R
Department of Vascular Research Akron City Hospital, Ohio 44309.
Ann Vasc Surg. 1990 Jul;4(4):344-9; discussion 349-50. doi: 10.1007/BF02000497.
Heparin is routinely added to vascular cell cultures to inhibit smooth muscle cell proliferation. The in vivo effects of heparin upon atherogenesis have remained controversial, however. In this experiment 13 four-month-old, heritably hyperlipidemic, Watanabe rabbits were randomly assigned to three treatment groups: 1500 U heparin, 500 U heparin, or saline. An injection protocol was followed for nine months. The rabbits were bled monthly from their marginal ear veins and plasma from these bleeds was analyzed for cholesterol and triglyceride content. At sacrifice each rabbit's aorta was sampled at 10 specific locations from the arch to the iliac bifurcation. The reduction in the area of the aorta by atherosclerotic plaque at each site was calculated using a video imaging system. Heparin injections significantly reduced mean plasma levels of cholesterol and triglycerides compared to pretreatment levels and saline injected controls. However, the magnitude of the reduction was not dose-related. The aortic luminal area occupied by atherosclerotic plaque in rabbits injected with 1500 U of heparin was significantly less (p less than .05) than in rabbits injected with saline or 500 U of heparin. Plaques from heparin-treated animals contained more fatty deposits and foam cells compared to the plaques from saline-treated rabbits which were more fibromuscular in organization. We conclude that heparin modulates the occurrence and composition of atherosclerotic plaques in this animal model of naturally occurring atherogenesis.
肝素通常添加到血管细胞培养物中以抑制平滑肌细胞增殖。然而，肝素在体内对动脉粥样硬化形成的影响一直存在争议。在本实验中，13只4个月大、遗传性高脂血症的渡边兔被随机分为三个治疗组：1500单位肝素组、500单位肝素组或生理盐水组。按照注射方案进行了9个月的实验。每月从兔的耳缘静脉取血，分析这些血液中的血浆胆固醇和甘油三酯含量。处死时，从每只兔的主动脉从弓部到髂动脉分叉处的10个特定位置取样。使用视频成像系统计算每个部位动脉粥样硬化斑块导致的主动脉面积减少量。与预处理水平和注射生理盐水的对照组相比，肝素注射显著降低了血浆胆固醇和甘油三酯的平均水平。然而，降低的幅度与剂量无关。注射1500单位肝素的兔主动脉腔内动脉粥样硬化斑块所占面积明显小于注射生理盐水或500单位肝素的兔（p小于0.05）。与组织更纤维肌性的生理盐水处理兔的斑块相比，肝素处理动物的斑块含有更多脂肪沉积物和泡沫细胞。我们得出结论，在这种自然发生动脉粥样硬化的动物模型中，肝素可调节动脉粥样硬化斑块的发生和组成。
