Blondeau N, Widmann C, Lazdunski M, Heurteaux C
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, UMR6097, 660, route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
Neuroscience. 2002;109(2):231-41. doi: 10.1016/s0306-4522(01)00473-0.
The findings reported in this work show that pretreatment with polyunsaturated fatty acids, particularly linolenic acid, present in vegetable oils, can provide a potent tolerance against neurodegeneration in two models of neuronal death-generating treatments such as kainic acid injection and global ischemia. Rats were injected i.v. with 500 nmol/kg of linolenic acid as long as 3 days prior to 6 min global ischemia or received an injection of linolenic acid as long as 3 days prior to a dose of 7.5 mg/kg kainic acid. Neuronal degeneration, assessed by analysis of neuronal density on Cresyl Violet-stained hippocampal sections, was significantly reduced in linolenic acid-treated rats (94-85% of cell survival in the ischemic model and 99-79% of cell survival in the epileptic model in respective CA1 and CA3 subfields). The neuroprotection observed following the injection of linolenic acid 3 days prior to induction of a severe ischemic or epileptic challenge was associated with the induction of the neuroprotective HSP70 heat shock protein within the time window of protection. The injection of 500 nmol/kg of linolenic acid induced a maximal HSP70 expression of 387% at 72 h. In contrast, the overexpression of one well-known protein inducer of neuronal cell death, Bax, which is induced by both ischemic and kainic acid-induced epileptic insults, was prevented by linolenic acid in the 3-day window of protection. These results strengthen the idea of an interesting potential therapeutical value of polyunsaturated fatty acids in neuronal protection.
这项工作中报告的研究结果表明，用植物油中存在的多不饱和脂肪酸，特别是亚麻酸进行预处理，可以在两种导致神经元死亡的治疗模型（如注射海藻酸和全脑缺血）中提供强大的抗神经退行性变能力。在全脑缺血6分钟前长达3天的时间里，给大鼠静脉注射500 nmol/kg的亚麻酸，或者在注射7.5 mg/kg海藻酸前长达3天的时间里给大鼠注射亚麻酸。通过对甲酚紫染色的海马切片上的神经元密度进行分析来评估神经元变性，结果显示，经亚麻酸处理的大鼠的神经元变性显著减少（在缺血模型中，CA1和CA3子区域的细胞存活率分别为94%-85%；在癫痫模型中，细胞存活率分别为99%-79%）。在诱导严重缺血或癫痫攻击前3天注射亚麻酸后观察到的神经保护作用，与在保护时间窗内诱导神经保护性热休克蛋白HSP70有关。注射500 nmol/kg的亚麻酸在72小时时诱导HSP70的最大表达为387%。相比之下，在3天的保护期内，亚麻酸可防止由缺血和海藻酸诱导的癫痫损伤所诱导的一种著名的神经元细胞死亡蛋白诱导剂Bax的过度表达。这些结果强化了多不饱和脂肪酸在神经元保护方面具有潜在治疗价值这一有趣观点。
