Division of Pharmacology, Central Drug Research Institute, 1. M.G. Marg, Lucknow, UP 226001, India.
J Physiol Biochem. 2011 Jun;67(2):205-16. doi: 10.1007/s13105-010-0065-z. Epub 2011 Feb 1.
The present study was undertaken to assess the chronology of major pathological events associated with high cholesterol (HC) diet and their modulation by anti-platelet drugs. Male Golden Syrian hamsters were fed HC diet up to 90 days. Plasma lipid, glucose and coagulation parameters (commercial kits), platelet activation (whole blood aggregation and static adhesion), endothelial dysfunction (aortic ring vasoreactivity), splenocyte TNF-α, IFN-γ and iNOS mRNA transcripts (RT-PCR), and ferric chloride (time to occlusion) induced thrombosis were monitored at 15, 30, 60, and 90 days after HC feeding and compared with normolipidemic hamsters. A significant increase in plasma lipid levels was observed at 15 days of HC feeding, but other parameters remain unaltered. Enhanced ADP, collagen, and thrombin-induced platelet aggregation, splenocyte TNF-α expression along with endothelial dysfunction were observed from 30 to 90 days of HC feeding. Platelet adhesion on collagen-/fibrinogen-coated surface and IFN-γ expression were augmented only after 60 days, while enhanced iNOS expression, reduction in thrombin time, and potentiation of ferric chloride-induced thrombosis was observed only at 90 days of HC feeding. Thus, pathological changes induced by HC diet depend on the duration and extent of hyperlipidemia. Moreover, hamsters treated with anti-platelet drugs aspirin (5 mg/kg) or clopidogrel (10 mg/kg) along with HC feeding exhibited reduction in platelet activation as well as subsequent changes observed in the abovementioned parameters following HC feeding. Since reduction in TNF-α was associated with reversion in endothelial dysfunction and prothrombotic state, the role of platelets is implicated in the pathological changes associated with HC feeding.
本研究旨在评估与高胆固醇（HC）饮食相关的主要病理事件的发生时间及其与抗血小板药物的调节关系。雄性金黄叙利亚仓鼠喂食 HC 饮食长达 90 天。在 HC 饮食喂养 15、30、60 和 90 天后，监测血浆脂质、葡萄糖和凝血参数（商业试剂盒）、血小板活化（全血聚集和静态粘附）、内皮功能障碍（主动脉环血管反应性）、脾细胞 TNF-α、IFN-γ 和 iNOS mRNA 转录物（RT-PCR）以及氯化铁（闭塞时间）诱导的血栓形成，并与正常脂质血症的仓鼠进行比较。在 HC 饮食喂养 15 天时观察到血浆脂质水平显著升高，但其他参数保持不变。从 30 天到 90 天的 HC 饮食喂养期间观察到 ADP、胶原和凝血酶诱导的血小板聚集增强，脾细胞 TNF-α表达以及内皮功能障碍。在 60 天后观察到血小板在胶原/fibrinogen 涂层表面的粘附和 IFN-γ表达增强，而仅在 90 天的 HC 饮食喂养后观察到 iNOS 表达增强、凝血酶时间缩短和氯化铁诱导的血栓形成增强。因此，HC 饮食引起的病理变化取决于高血脂的持续时间和程度。此外，与 HC 饮食喂养同时给予抗血小板药物阿司匹林（5mg/kg）或氯吡格雷（10mg/kg）治疗的仓鼠表现出血小板活化减少，以及随后在 HC 饮食喂养后观察到的上述参数的变化减少。由于 TNF-α 的减少与内皮功能障碍和促血栓形成状态的逆转相关，因此血小板在与 HC 饮食相关的病理变化中发挥作用。
