6-羟基多巴胺和MK-801抑制脊髓水肿的效应(英文)

Inhibitory effect of 6-hydroxy dopamine and MK-801 on spinal cord edema

背景:脊髓遭受急性损伤后,脊髓水肿是引发和加重脊髓组织病理改变的重要因素。去甲肾上腺素在损伤后立即引起微血管的收缩、内皮损伤、动脉通透性的增加,被认为是参与水肿。近年来许多研究发现,兴奋性氨基酸与细胞水肿有关。目的:观察选择性酚胺能神经元破坏剂、6-羟基多巴胺和天门冬氨酸的竞争性拮抗剂对脊髓急性损伤后发生水肿时的作用及其机制。设计:随机对照实验研究。单位:河北医科大学第三医院脊柱外科。材料:实验于2003-03/09在河北医科大学第三医院实验动物中心完成。实验选用Wistar大鼠160只,体质量300～350g,雌雄不限,将所有大鼠随机分为3组,6-羟基多巴胺组60只,MK-801(5-甲基二氢二苯并环庚烯亚胺马来酸)组50只,对照组50只。方法:采用静力加载技术在Wistar大鼠T13椎体水平造成急性脊髓损伤。6-羟基多巴胺组在蛛网膜下腔注射6-羟基多巴胺,MK-801组在尾静脉注射MK-801治疗,对照组大鼠不给予治疗。应用神经学功能评分、组织含水量测定及光镜、电镜观察,比较各组间的水肿程度。主要观察指标:神经学功能评分及脊髓组织含水量。结果:160只大鼠纳入结果分析。①6-羟基多巴胺组伤后髓内去甲肾上腺素含量明显下降,由(217.45±4.26)ng/g降到(29.37±2.61)ng/g,差异有显著性意义(P<0.01)。对脊髓组织水肿的有效抑制达24h,伤后12h可观察到明显的功能恢复,血管源性水肿表现最轻。②MK-801组伤后24h才表现为对水肿的抑制,神经功能在伤后早期恢复较对照组差异不显著(P>0.05),伤后24h有明显的功能恢复(P<0.05),细胞毒性水肿表现最轻。结论:去甲肾上腺素可以抑制脊髓损伤后早期发生的血管源性水肿,兴奋性氨基酸可以抑制稍后发生的细胞毒性水肿。

BACKGROUND： After acute spinal cord injury （SCI）, edema of spinal cord is an important factor for inducing and deteriorating pathological changes of spinal cord tissue. After injury, noredrenaline （NE） instantly causes microvascular contraction, endothelial injury, increase of arterial permeability and participation in edema. Recently, many researches suggest that excitatory amino acids （F_AA） are related to cellular edema. OBJECTIVE： To study the effect and mechanism of selective phenol aminergic neuron, 6-hydroxy dopamine （6-OHNA） and aspartic acid （ASP） on edema after acute SCI. DESIGN： Randomized controlled study SETTING ： Department of Spine Surgery, the Third Hospital of Hebei Medical University MATERIALS ： The experiment was carried out at the Experimental Animal Center of the Third Hospital of Hebei Medical University from March to September 2003. A total of 160 Wistar rats weighing 300-350 g of both genders were randomly divided into three groups： 6-OHNA group （n =60）, MK-801 group （n =50） and control group （n =50）. METHODS： Acute SCI was induced at the level of T13 vertebral body with the static load technique. Rats in 6-OHNA group were injected with 6-OHNA into subarachnoid space; rats in MK-801 group were injected with MK-801 into caudal vein; rats in control group did not receive any treatment. The extent of edema was compared in the three groups by means of neurological scoring, water content measurement, light microscopy and electron microscopy. MAIN OUTCOME MEASURES： Neurological scores and water content RESULTS： All 160 rats were involved in the final analysis. （1） After SCI, content of NE in 6-OHNA group was decreased from （217.45±4.26） ng/g to （29.37±2.61） ng/g, and the difference was significant （P〈 0.01）. Edema in spinal cord tissue was effectively inhibited for 24 hours. At 12 hours after SCI, function recovered remarkably and vascular-derived edema was the mildest. （2） In MK-801 group, there was no significant suppression of the edema until 24 hours after injury. Early recovery of neurological function was not significantly different from that in control group （P 〉 0.05）, but functional recovery was obvious until 24 hours after injury （P 〈 0.05）. The degree of cytotoxic edema was the Iightest. CONCLUSION： NE can inhibit vascular-derived edema at early phase of SCI, and EAA can inhibit cytotoxic edemas which develops at a relatively later stage.