Winocour P D, Rand M L, Kinlough-Rathbone R L, Richardson M, Mustard J F
Department of Pathology, McMaster University, Hamilton, Ont., Canada.
Atherosclerosis. 1989 Mar;76(1):63-70. doi: 10.1016/0021-9150(89)90194-9.
Platelets from rats with genetically determined hypercholesterolaemia are hypersensitive to aggregation induced by thrombin compared with platelets from their genetic controls without hypercholesterolaemia. Aggregation or release induced by thrombin of platelets from hypercholesterolaemic and control rats correlated significantly with plasma cholesterol concentrations. Platelet responses to ADP or collagen were not different between the groups. The hypersensitivity to thrombin-induced aggregation was independent of released ADP or products of arachidonic acid metabolism. The changes in platelet sensitivity occurred with only moderate increases in plasma cholesterol concentration and with no detectable changes in total platelet cholesterol. The hypersensitivity of platelets from hypercholesterolaemic rats was not associated with a reduction in platelet survival or any significant injury to the aortic endothelium in these animals. Platelets from hypercholesterolaemic rats were smaller than platelets from controls. Thus, platelets from rats with genetically determined hypercholesterolaemia have alterations in function similar to those found with platelets from rats with diet-induced hypercholesterolaemia indicating that this strain can be used to study the mechanisms by which cholesterol can change platelet function without the possible complicating effects of dietary factors. Since platelet hypersensitivity occurred in rats with genetically determined hypercholesterolaemia without a reduction in platelet survival, these studies are also consistent with the reduced platelet survival found in animals with diet-induced hypercholesterolaemia being independent of platelet changes.
与无高胆固醇血症的遗传对照大鼠的血小板相比，具有遗传决定的高胆固醇血症大鼠的血小板对凝血酶诱导的聚集更为敏感。高胆固醇血症大鼠和对照大鼠的血小板由凝血酶诱导的聚集或释放与血浆胆固醇浓度显著相关。两组之间血小板对ADP或胶原的反应没有差异。对凝血酶诱导聚集的超敏反应与释放的ADP或花生四烯酸代谢产物无关。血小板敏感性的变化仅在血浆胆固醇浓度适度升高时出现，且总血小板胆固醇无可检测到的变化。高胆固醇血症大鼠血小板的超敏反应与这些动物血小板存活时间缩短或主动脉内皮的任何显著损伤无关。高胆固醇血症大鼠的血小板比对照大鼠的血小板小。因此，具有遗传决定的高胆固醇血症大鼠的血小板功能改变与饮食诱导的高胆固醇血症大鼠的血小板功能改变相似，这表明该品系可用于研究胆固醇改变血小板功能的机制，而无饮食因素可能带来的复杂影响。由于在具有遗传决定的高胆固醇血症大鼠中出现了血小板超敏反应，而血小板存活时间并未缩短，这些研究也与饮食诱导的高胆固醇血症动物中发现的血小板存活时间缩短独立于血小板变化这一现象相一致。
