Hirosumi J, Nomoto A, Ohkubo Y, Sekiguchi C, Mutoh S, Yamaguchi I, Aoki H
Atherosclerosis. 1987 Apr;64(2-3):243-54. doi: 10.1016/0021-9150(87)90252-8.
Cuff-treatment of the rabbit carotid artery produced a diffuse intimal thickening which resembled early lesions of atherosclerosis. A limited amount of focal endothelial damage occurred first (0.5 h), leukocytes infiltrated the subendothelium and extensive endothelial denudation occurred at 24 h. At 3 days, the regenerating endothelium covered the denuded area, and the media was edematous. At 7 days proliferation of intimal cells became visible. Maximum intimal thickening occurred at 3 weeks. Daily injection of dexamethasone (0.01-10 mg/kg i.m.) and ticlopidine (1-100 mg/kg i.m.) dose-dependently attenuated the intimal thickening. Indomethacin had little effect. Inflammatory exudate from zymosan-activated air pouch induced chemotaxis of rat smooth muscle cells (SMC) in vitro. Similar chemotactic activity was observed with leukotriene B4 (LTB4) but not with the other lipoxygenase products tested. The exudate contained reasonable amounts of LTB4, which would account for its chemotactic activity. Dexamethasone inhibited the chemotaxis by the exudate and proliferation of SMC. These results are discussed in relation to the mechanism of atherogenesis. It is concluded that leukocytes play a major role in cuff-induced intimal thickening, and that their products cause endothelial denudation and SMC chemotaxis. Involvement of platelet aggregation in atherogenesis is also suggested.
对兔颈动脉进行套扎处理会导致弥漫性内膜增厚，这类似于动脉粥样硬化的早期病变。首先会出现少量局灶性内皮损伤（0.5小时），白细胞浸润至内皮下，24小时时会出现广泛的内皮剥脱。3天时，再生的内皮覆盖剥脱区域，且中膜水肿。7天时，内膜细胞增殖变得明显。内膜增厚在3周时达到最大值。每日注射地塞米松（0.01 - 10毫克/千克，肌肉注射）和噻氯匹定（1 - 100毫克/千克，肌肉注射）可剂量依赖性地减轻内膜增厚。吲哚美辛作用甚微。酵母聚糖激活的气囊肿的炎性渗出物在体外可诱导大鼠平滑肌细胞（SMC）的趋化性。白三烯B4（LTB4）也观察到类似的趋化活性，但所测试的其他脂氧合酶产物则未观察到。渗出物中含有适量的LTB4，这可以解释其趋化活性。地塞米松抑制渗出物诱导的趋化性以及SMC的增殖。结合动脉粥样硬化的发病机制对这些结果进行了讨论。得出的结论是，白细胞在套扎诱导的内膜增厚中起主要作用，并且它们的产物导致内皮剥脱和SMC趋化。还提示血小板聚集参与了动脉粥样硬化的发生。
