Docosahexaenoic acid complexed to albumin elicits high-grade ischemic neuroprotection
Docosahexaenoic acid complexed to albumin elicits high-grade ischemic neuroprotection
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DOI：
10.1161/01.str.0000149620.74770.2e
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发表时间：
2005-01-01
期刊：
影响因子：
8.3
通讯作者：
Bazan, NG
中科院分区：
文献类型：
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作者：
Belayev, L;Marcheselli, VL;Bazan, NG
背景和目的-大剂量人血白蛋白治疗在脑缺血和创伤模型中具有很强的神经保护作用，目前正在进行中试性临床卒中试验。在其缺血作用中，白蛋白诱导n-3多不饱和脂肪酸的全身动员，并可能有助于补充从神经膜丢失的多不饱和脂肪酸。（DHA; 22：6 n-3），并比较其与天然白蛋白在由管腔内缝合产生的2小时局灶性缺血大鼠中的神经保护作用。结果-在用DHA -白蛋白0.63g/kg治疗的动物中，72小时神经行为评分的改善显著超过其他治疗组，以及组织保护的程度（皮质梗死减少86%）具有高度显著性，并且倾向于超过1.25 g/kg天然白蛋白（65%）产生的皮质保护程度。DHA -白蛋白0.63 g/kg，而不是天然白蛋白，也显着减少皮质下梗死和显着减少脑肿胀。DHA -白蛋白处理的缺血后脑的脂质组学分析揭示了神经保护性DHA代谢物10，17 S-二十二碳三烯的大量积累，结论-DHA提供的高级神经保护作用-在相对低的白蛋白剂量下的白蛋白复合物在临床上是有利的，因为它可以降低急性血管内容量超负荷和充血性心力衰竭的可能性，用高剂量白蛋白治疗心血管功能受损的患者。
Background and Purpose - High-dose human albumin therapy is strongly neuroprotective in models of brain ischemia and trauma and is currently being studied in a pilot-phase clinical stroke trial. Among its actions in ischemia, albumin induces the systemic mobilization of n-3 polyunsaturated fatty acids and may help to replenish polyunsaturated fatty acids lost from neural membranes.Methods - We complexed 25% human albumin to docosahexaenoic acid (DHA; 22: 6n-3) and compared its neuroprotective efficacy with that of native albumin in rats with 2-hour focal ischemia produced by intraluminal suture-occlusion of the middle cerebral artery.Results - In animals treated with DHA - albumin, 0.63 g/kg, the improvement in neurobehavioral scores at 72 hours significantly exceeded that of other treatment groups, and the extent of histological protection (86% reduction in cortical infarction) was highly significant and tended to surpass the degree of cortical protection produced by native albumin at 1.25 g/kg (65%). DHA - albumin 0.63 g/kg, but not native albumin, also significantly reduced subcortical infarction and markedly diminished brain swelling. Lipidomic analysis of DHA - albumin-treated postischemic brains revealed a large accumulation of the neuroprotective DHA metabolite, 10,17S-docosatriene, in the ipsilateral hemisphere.Conclusions - The high-grade neuroprotection afforded by the DHA - albumin complex at relatively low albumin doses is clinically advantageous in that it might reduce the likelihood of acute intravascular volume overload and congestive heart failure sometimes induced when patients with compromised cardiovascular function are treated with high-dose albumin.