Hamann Gerhard F, Burggraf Dorothe, Martens Helge K, Liebetrau Martin, Jäger Gabriele, Wunderlich Nathalie, DeGeorgia Michael, Krieger Derk W
Department of Neurology, Ludwig-Maximilians University, Munich, Germany.
Stroke. 2004 Mar;35(3):764-9. doi: 10.1161/01.STR.0000116866.60794.21. Epub 2004 Feb 19.
Microvascular basal lamina damage occurs after cerebral ischemia and is important for the development of hemorrhage. The aim of this study was to determine whether hypothermia could maintain microvascular integrity in ischemic stroke.
Using the suture model, we subjected 12 rats to 3 hours of focal ischemia and 24 hours of reperfusion. Six rats received postischemic normothermia (37 degrees C) and 6 received hypothermia (32 degrees C to 34 degrees C) for the reperfusion period; a group of 6 sham-operated animals without ischemia was used as control. Collagen type IV and hemoglobin were measured by Western blot analysis, matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography, and urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) by plasminogen-casein zymography.
Hypothermia reduced basal lamina collagen type IV loss: 87+/-16% (hypothermia) versus 43+/-4% (normothermia) in basal ganglia and 74+/-16% versus 64+/-4% in cortex; hypothermia reduced hemorrhage from 431+/-65% (normothermia) to 241+/-28% (basal ganglia) (P<0.05). Hypothermia also reduced MMP-2, MMP-9, uPA, and tPA (basal ganglia: MMP-2: 71+/-20% [hypothermia] versus 109+/-3% [normothermia]; MMP-9: 38+/-12% versus 115+/-4%; uPA activity: 310+/-86% versus 1019+/-22%; tPA activity: 61+/-17% versus 111+/-13%; cortex: MMP-2: 53+/-6% versus 116+/-1%; MMP-9: 16+/-4% versus 123+/-3%; uPA: 180+/-27% versus 176+/-10%; tPA: 91+/-15% versus 101+/-8%; each difference: P<0.001) (nonischemic control side=100%).
Hypothermia maintains microvascular integrity and reduces hemorrhage and the activities of MMP-2, MMP-9, uPA, and tPA.
脑缺血后微血管基底膜受损，这对出血的发生发展至关重要。本研究旨在确定低温是否能维持缺血性卒中时的微血管完整性。
采用栓线模型，对12只大鼠进行3小时的局灶性缺血及24小时的再灌注。6只大鼠在再灌注期接受缺血后常温（37℃）处理，6只接受低温（32℃至34℃）处理；另取6只未进行缺血手术的假手术动物作为对照组。通过蛋白质免疫印迹分析测定IV型胶原和血红蛋白，用明胶酶谱法测定基质金属蛋白酶（MMP）-2和MMP-9，用纤溶酶原-酪蛋白酶谱法测定尿激酶型纤溶酶原激活剂（uPA）和组织型纤溶酶原激活剂（tPA）。
低温减少了基底膜IV型胶原的丢失：在基底节区，低温组为87±16%，常温组为43±4%；在皮质，低温组为74±16%，常温组为64±4%；低温使出血从常温组的431±65%降至241±28%（基底节区）（P<0.05）。低温还降低了MMP-2、MMP-9、uPA和tPA的水平（基底节区：MMP-2：低温组为71±20%，常温组为109±3%；MMP-9：38±12%，常温组为115±4%；uPA活性：310±86%，常温组为1019±22%；tPA活性：61±17%，常温组为111±13%；皮质：MMP-2：53±6%，常温组为116±1%；MMP-9：16±4%，常温组为123±3%；uPA：180±27%，常温组为176±10%；tPA：91±15%，常温组为101±8%；每组差异：P<0.001）（非缺血对照侧=100%）。
低温可维持微血管完整性，减少出血以及MMP-2、MMP-9、uPA和tPA的活性。
