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多不饱和脂肪酸通过TREK-1钾通道发挥脑血管舒张剂的作用。

Polyunsaturated fatty acids are cerebral vasodilators via the TREK-1 potassium channel.

作者信息

Blondeau Nicolas, Pétrault Olivier, Manta Stella, Giordanengo Valérie, Gounon Pierre, Bordet Régis, Lazdunski Michel, Heurteaux Catherine

机构信息

Institut de Pharmacologie Moléculaire et Cellulaire, UMR 6097, CNRS Université de Nice Sophia Antipolis, Institut Paul Hamel, Valbonne, France.

出版信息

Circ Res. 2007 Jul 20;101(2):176-84. doi: 10.1161/CIRCRESAHA.107.154443. Epub 2007 Jun 7.

Abstract

Vessel occlusion is the most frequent cause for impairment of local blood flow within the brain resulting in neuronal damage and is a leading cause of disability and death worldwide. Polyunsaturated fatty acids and especially alpha-linolenic acid improve brain resistance against cerebral ischemia. The purpose of the present study was to evaluate the effects of polyunsaturated fatty acids and particularly alpha-linolenic acid on the cerebral blood flow and on the tone of vessels that regulate brain perfusion. alpha-Linolenic acid injections increased cerebral blood flow and induced vasodilation of the basilar artery but not of the carotid artery. The saturated fatty acid palmitic acid did not produce vasodilation. This suggested that the target of the polyunsaturated fatty acids effect was the TREK-1 potassium channel. We demonstrate the presence of this channel in basilar but not in carotid arteries. We show that vasodilations induced by the polyunsaturated fatty acid in the basilar artery as well as the laser-Doppler flow increase are abolished in TREK-1(-/-) mice. Altogether these data indicate that TREK-1 activation elicits a robust dilation that probably accounts for the increase of cerebral blood flow induced by polyunsaturated fatty acids such as alpha-linolenic acid or docosahexanoic acid. They suggest that the selective expression and activation of TREK-1 in brain collaterals could play a significant role in the protective mechanisms of polyunsaturated fatty acids against stroke by providing residual circulation during ischemia.

摘要

血管阻塞是导致脑内局部血流受损从而造成神经元损伤的最常见原因,并且是全球范围内致残和死亡的主要原因。多不饱和脂肪酸,尤其是α-亚麻酸,可提高大脑对脑缺血的抵抗力。本研究的目的是评估多不饱和脂肪酸,特别是α-亚麻酸对脑血流量以及调节脑灌注的血管张力的影响。注射α-亚麻酸可增加脑血流量,并引起基底动脉而非颈动脉的血管舒张。饱和脂肪酸棕榈酸不会产生血管舒张作用。这表明多不饱和脂肪酸作用的靶点是TREK-1钾通道。我们证明了该通道存在于基底动脉而非颈动脉中。我们发现,在TREK-1基因敲除小鼠中,多不饱和脂肪酸在基底动脉中诱导的血管舒张以及激光多普勒血流增加均被消除。这些数据共同表明,TREK-1的激活会引发强烈的血管舒张,这可能解释了由α-亚麻酸或二十二碳六烯酸等多不饱和脂肪酸诱导的脑血流量增加。它们表明,TREK-1在脑侧支中的选择性表达和激活可能在多不饱和脂肪酸对中风的保护机制中发挥重要作用,即在缺血期间提供残余循环。

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