格列本脲对大鼠皮层扩散性抑制中脑血管的调节作用

Regulation of Pial Artery by Glibenclamide During Cortical Spreading Depression in Rats

皮层扩散性抑制(corticalspreadingdepression,CSD)是研究偏头痛、脑梗塞等疾病的重要病理模型.已有研究表明,在普遍被观察到的CSD过程中软脑膜动脉血管大幅度舒张之前,还存在一个较小幅度的软脑膜动脉扩张和收缩.但其中的脑血管调节机制尚不清楚.采用550nm的内源信号光学成像(opticalintrinsicsignalimaging,OISI)监测ATP敏感钾离子通道(ATP-sensitivepotassiumchannels,KATP)的阻断剂格列本脲(glibenclamide,glyb),对针刺诱导的大鼠CSD过程中软脑膜动脉血管舒缩过程的影响.实验中观测到软脑膜血管的初始小收缩(initialslightconstriction,ISC)相对于对照组显著减弱,其中应用10μmol/Lglyb时,74.5%的ISC被完全抑制,100μmol/Lglyb时则有96.2%的ISC完全消失.相对于CSD发生前,软脑膜动脉血管大幅舒张(largedilation,LD)的峰值也分别显著增强了(53.8±19.3)%和(59.8±19.6)%.结果表明,可能是神经元上的KATP在CSD过程中被glyb阻断从而抑制了软脑膜动脉血管的收缩.

Cortical spreading depression （CSD） is an important disease model for migraine and stroke. Previous studies showed that before the pial artery large dilation which were widely observed in CSD, there is also a small constriction occurring in pial arteres. However, the mechanisms contributing to the regulation of this cerebrovascular response remain unknown. Optical intrinsic signal imaging（OISI） at 550 nm wavelength was used to monitor the responses of the pial arteries during pinprick induced CSD following the application of a KATP antagonist glibenclamide （glyb）. By applying the glyb, the initial slight constriction （ISC） is obviously reduced, most of the ISC （10 μmol/L： 74.5%; 100 μmol/L： 96.2%） even completely restrained. And the peak of large dilation （LD） in response to the pial arteries was enhanced to （53.8± 19.3） % and （59.8± 19.6） % of the control with 10 μmol/L and 100 μmol/L glyb, respectively. It can be suggested that KATP in nerve cells of pre and post-synaptically plays a lead role in inhibiting CSD-associated hyperemia.