mito K_(ATP)和κ-阿片受体介导肢体缺血后处理对抗大鼠脑缺血/复灌损伤  

mito K_(ATP) AND κ-OPIOID RECEPTOR MEDIATE THE NEUROPROTECTIVE EFFECT OF LIMB ISCHEMIC POST-CONDITIONING ON RAT BRAIN ISCHEMIA/REPERFUSION INJURY

作　　者：沈佳[1] 孙丽娜[1] 吴莉萍[1] 夏强[1] 

机构地区：[1]浙江大学医学院生理学系,浙江杭州310058

出　　处：《中国应用生理学杂志》2009年第3期368-372,共5页Chinese Journal of Applied Physiology

摘　　要：目的:观察肢体缺血后处理(LIPC)在大鼠局灶性脑缺血/复灌损伤中的神经保护作用及其作用机制。方法:将大鼠随机分为6组:空白对照组,单侧LIPC组,双侧LIPC组(bLIPC),bLIPC+mito KATP阻断剂5-hydroxyde-canoate(5-HD)预处理组,bLIPC+κ-阿片受体拮抗剂nor-binaltorphimine(nor-BNI)预处理组,bLIPC+双侧后肢体外循环组。采用线栓法建立大鼠大脑中动脉栓塞(MCAO)模型,术后进行神经系统症状评分,血浆强啡肽和脑啡肽水平测定,大脑梗死面积测定。结果:单侧LIPC能改善大鼠局灶性脑缺血/复灌损伤后的神经系统功能评分(P<0.05),并减少大脑梗死面积(P<0.01);而双侧LIPC能显著提高大鼠局灶性脑缺血/复灌损伤后的神经系统功能评分,并显著减少大脑梗死面积(P<0.01),比单侧LIPC的作用更为明显(P<0.05)。双侧LIPC后5、15、30min,1和2h这五个时间点,血浆强啡肽水平显著增高(P<0.01),12和24h这两个时间点恢复至正常水平;而血浆脑啡肽水平的改变与双侧LIPC前比较无显著差异(P>0.05)。nor-BNI预处理(25nmol)和5-HD预处理(10mg/kg)均消除了双侧LIPC所致的神经系统功能评分增加和大脑梗死面积减少(P<0.01)。结论:LIPC在大鼠局灶性脑缺血/复灌损伤中具有显著的神经保护作用,其作用可能与LIPC诱导内源性阿片激动剂释放和激活mitoKATP有关。Aim： To observe the neuroprotective effect of limb ischemic post-conditioning（LIPC） on local brain ischemia and reperfusion injury in rat, and to investigate whether mitochondrial ATP sensitive potassium channel（mito KATP） and κ-opioid receptor were involved in the neuroprotection. Methods： Rats were randomly divided into 6 groups that were ischemia/reperfusion group, unilateral hindlimb ischemia group （uLIPC）, bilateral hindlimbs ischemia group （bLIPC）, bLIPC ＋ antagonist of κ-opioid receptor nor-binahorphimine （nor-BNI） group, bLIPC ＋ mito KATe blocker 5-hydroxydecanoate（5-HD） group, bLIPC ＋ extracorporeal circtilation of bilateral hindlimbs via femoral arteries（EC） group. Cerebral ischemia was induced by middle cerebral artery occlusion （MCAO）, neurological scores, plasma levels of dynorphin and enkephalin, the brain infarct areas were determined after reperfusion. Results： Unilateral LIPC partially improved the neurological score after local brain ischemia and reperfusion injury in rat（ P 〈 0.05）, and decreased the infarct area compared with the untreated group undergoing brain isehemia and reperfusion（ P 〈 0. 01 ）. Bilateral LIPC significantly improved the neurological score after local brain ischemia and reperfusion injury（ P 〈 0.01 ）, and decreased the infarct area （ P 〈 0.01 ）. The neurological scores of bilateral LIPC group were significant higher than those of unilateral LIPC（ P 〈 0.05）. The plasma level of dynorphin was significantly increased（ P 〈 0.01 ） at 5, 15, 30 min, 1 and 2 h after bilateral LIPC, however, it deceased to the normal level at 12 h after bilateral LIPC. The plasma level of enkephalin showed no obvious change after bilateral LIPC（ P 〉 0.05）. nor-BNI（25 nmol/L） and 5-HD（ 10 mg/kg） abolished the effect of bilateral LIPC（ P 〈 0.01 ）. Conclusion： LIPC protects rat from local brain ischemia and reperfusion injury, mito KATe may be involved in the neuroprotection, and κ-opioid recepto

关 键 词：肢体缺血后处理 局灶性脑缺A/复灌损伤 Κ-阿片受体 线粒体ATP敏感性钾通道 

分 类 号：R743.31[医药卫生—神经病学与精神病学]