Macrae I M, Robinson M J, Graham D I, Reid J L, McCulloch J
Wellcome Neuroscience Group, Wellcome Surgical Institute, and Hugh Fraser Neuroscience Laboratories, Glasgow, U.K.
J Cereb Blood Flow Metab. 1993 Mar;13(2):276-84. doi: 10.1038/jcbfm.1993.34.
The capacity of endothelin-1 to induce severe reductions in cerebral blood flow and ischaemic neuronal damage was assessed in anaesthetised rats. Endothelin-1 (25 microliters of 10(-7)-10(-4) M) was applied to the adventitial surface of an exposed middle cerebral artery and striatal blood flow assessed by the hydrogen clearance technique. Endothelin-1 induced severe dose-dependent reductions in cerebral blood flow (e.g., minimum CBF at 10(-5) M of 9 +/- 11 ml 100 g-1 min-1 compared to 104 +/- 22 ml 100 g-1 min-1 with vehicle, p < 0.05), which persisted for at least 60 min at each concentration of endothelin-1. Application of endothelin-1 to the middle cerebral artery produced dose-dependent ischaemic brain damage (e.g., volume of damage of 65 +/- 34 mm3 at 10(-5) M compared to 0.22 +/- 0.57 mm3 for vehicle, p < 0.01). These data demonstrate that endothelin-1 is capable of reducing blood flow to pathologically low levels and provide a new model of controlled focal ischaemia followed by reperfusion.
在麻醉大鼠中评估了内皮素 -1 导致脑血流量严重减少和缺血性神经元损伤的能力。将内皮素 -1（25微升10^(-7)-10^(-4)M）应用于暴露的大脑中动脉外膜表面，并通过氢清除技术评估纹状体血流量。内皮素 -1 引起脑血流量严重的剂量依赖性减少（例如，10^(-5)M时的最低脑血流量为9±11毫升100克^(-1)分钟^(-1)，而溶剂对照组为104±22毫升100克^(-1)分钟^(-1)，p<0.05），在每种内皮素 -1 浓度下至少持续60分钟。将内皮素 -1 应用于大脑中动脉会产生剂量依赖性的缺血性脑损伤（例如，10^(-5)M时损伤体积为65±34立方毫米，而溶剂对照组为0.22±0.57立方毫米，p<0.01）。这些数据表明内皮素 -1 能够将血流量降低到病理低水平，并提供了一种新的可控局灶性缺血再灌注模型。
