二氮嗪预处理对深低温停循环脑早期保护作用的实验研究  

The Study on Preconditioning with Diazoxide Ameliorates Neurological Injury in the Early Period Induced by Deep Hypothermic Circulatory Arrest

作　　者：高国栋[1] 潘心海[2] 张宽宏[2] 李明[3] 田良鑫[3] 郑军[3] 孙立忠[3] 龙村[1] 

机构地区：[1]中国医学科学院阜外心血管病医院体外循环科,北京市100037 [2]山东省临朐县人民医院 内科 [3]阜外心血管病医院外科

出　　处：《中国分子心脏病学杂志》2007年第1期39-42,共4页Molecular Cardiology of China

摘　　要：目的观察二氮嗪预处理对深低温停循环(DHCA)所致的脑损伤的早期保护作用,并探讨其可能机制。方法健康大耳白兔24只,随机分为3组,每组8只:对照组(安慰剂组):DHCA+安慰剂;实验组(二氮嗪组):DHCA+二氮嗪(二氮嗪5 mg/kg,CPB前15 min静脉注入);拮抗剂组(5-HD组):DHCA+5-HD(20 mg/kg,给予二氮嗪前静脉注入)+二氮嗪(5 mg/kg,CPB前15 min静脉注入)。每组均经CPB降温至鼻咽温18℃,停循环60 min,复温,停机,取脑组织。观察指标为脑组织含水量、脑组织匀浆中兴奋性氨基酸(EAA)及丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性的变化,并制作电镜标本行透射电镜观察脑组织超微结构的改变。结果实验组脑组织含水量及MDA含量明显低于对照组(P＜0．05b)及拮抗剂组(P＜0．05);实验组EAA含量及SOD活性明显高于对照组(P＜0．01)及拮抗剂组(P＜0．05);拮抗剂组各项指标与对照组比无统计学意义(P＞0．05);电镜结果示各组脑细胞超微结构明显损伤,总体印象实验组各种神经元细胞器损伤较上述组有所减轻。结论二氮嗪预处理对DHCA引起的神经元损伤具有早期保护作用。Objective To investigate whether preconditioning with diazoxide could ameliorate the cerebral injuries induced by deep hypothermic circulatory arrest （DHCA）. Metheds Twenty-four rabbits weighting 2.3 - 2.8 kg were randomly allocated to 3 groups, each group consists of eight rabbits. One group served as control： received DHCA and vehicle. In experiment group animals received DHCA and precondi- tioning with diasoxide （5 mg/kg bolus 15 minutes prior to CPB） . In antagonist group animals received DH- CA ,preconditioning with diasoxide （5 mg/kg, bolus 15 minutes prior to CPB ） and mitOKsTP antagonists, 5- hydroxydecanoic acid （5-HD, 20 mg/kg, before diasoxide administration）. Each group where placed on cardiopulmonary bypass （CPB） and cooled to 18℃. After 60 mimers of DHCA, animals were rewarmed and weaned from CPB. All animals were executed at the end of experience and brain was removed for ultrastrucrure examination and to measure the content of water, excitatory amino acids （EAAs）, malondialdehyde （MDA） and superoxide dismutase （SOD） activity in brain tissue. Results In experiment group, the content of EAAs and the activity of SOD increased significantly , the level of the content of water and the content of MDA in brain tissue decreased significantly as compared with that in control group （ P 〈 0.05） and antagonist group （ P 〈 0.05） . Distinct cerebral untrastructural injuries were seen in the three groups on transmission microscopy. Overall quality level, the injury in control group and in antagonist group was more severe than that in experiment group. Conclusions Preconditioning with diasoxide protects brain from ischemia-reperfusion injury induced by DHCA. This suggests that pharmacologic preconditioning with the mitoKATP chanel opener diazoxide may offer effective neuroprotection during DHCA.

关 键 词：二氮嗪 预处理 深低温停循环 丙二醛 兴奋性氨基酸 超氧化物歧化酶 

分 类 号：R741[医药卫生—神经病学与精神病学]