线粒体ATP敏感性钾离子通道参与远程预处理对大鼠脑保护作用的机制  

Neuroprotection of remote preconditioning via activation of mitochondrial ATP-sensitive potassium channel after focal cerebral ischemia in rats

作　　者：赵翚[1] 董海龙[1] 熊利泽[1] 路志红[1] 孙静[1] 徐宁[1] 

机构地区：[1]第四军医大学西京医院麻醉科,陕西西安710033

出　　处：《第四军医大学学报》2007年第18期1633-1635,共3页Journal of the Fourth Military Medical University

基　　金：国家自然科学基金(30300329)

摘　　要：目的:探讨线粒体ATP敏感性钾离子通道在远程预处理对大鼠脑保护效应中的作用.方法:SD雄性大鼠,随机分为4组(每组n=10):①RPC+NS组,行远程预处理前15min,给予生理盐水1mL静脉注射,远程预处理1h后行MCAO;②RPC+5-HD组,行远程预处理前15min给予5-羟基葵酸盐(5-HD)10mg/kg静脉注射,远程预处理后1h行MCAO;③DIAZ组,MCAO前30min给予二氮嗪(DIAZ)5mg/kg腹腔注射;④DMSO组,MCAO前30min给予5g/LDMSO.所有大鼠行MCAO模型阻闭120min恢复再灌注,观察再灌注后24h时神经功能损害并取大脑行TTC染色测量脑梗死容积百分比.结果:①神经功能障碍评分:再灌注24h后神经功能障碍评分,RPC+NS组和DIAZ组与RPC+5-HD组和DMSO组相比有统计学差异(P<0.05),RPC+5-HD组和DMSO组相比无统计学差异(P>0.05).②脑梗死容积百分比:再灌注24h后脑梗死容积百分比RPC+NS组[(16.3±2.9)%,P=0.00]和DIAZ组[(17.5±8.9)%,P=0.00]明显小于RPC+5-HD组(46.1±10.1)%和DMSO组(36.4±10.9)%,而DMSO组和RPC+5-HD组相比较无统计学差异(P=0.216),RPC+NS组和DIAZ组相比较无统计学差异(P=0.747).结论:线粒体敏感性钾离子通道阻断剂可阻断远程预处理保护作用,提示线粒体敏感性钾离子通道参与远程预处理对大鼠脑缺血耐受的形成机制.AIM： To investigate whether the neuroprotection effect of remote preconditioning（RPC） is dependent on mitochondrial adenosine triphosphate （ATP）-sensitive potassium channel in transient focal cerebral ischemia-reperfusion model in rats. METHODS： Forty male SD rats weighing （300 ± 20） g were randomly allocated to 4 groups （ n = 10 ）. RPC ＋ NS group ： the rats were intravenously injected with 1 mL saline 15 min before RPC and middle cerebral artery occlusion （MCAO） was performed 1 h after RPC; RPC ＋ 5-HD group： the rats were intravenously injected with 5-HD（ 10 mg/kg） 15 min before RPC and MCAO was performed 1 h after RPC ; DIAZ Group ： 30 rain before MCAO, the rats were intraperitoneally administered with diazoxide （DIAZ 5 mg/kg） 30 min before MCAO without RPC; DMSO group： the rats were intraperitoneally administered with 5 g/L dimethyl sulfoxide （DMSO） 30 min before MCAO. MCAO was induced by occluding the right middle cerebral artery for 120 min. Neuroligical deficit score （NDS）and brain infarct volume were evaluated at 24 h after reperfusion. RESULTS： ① The NDS in RPC ＋ NS and DIAZ group were better than those in RPC ＋ 5-HD group and DMSO group （ P 〈 0.05 ）. There was no significant difference in NDS between RPC ＋ 5-HD group and DMSO group （P 〉 0. 05 ）.② The infarct volume percentage in RPC ＋ NS （16.3 ±2.9）% and DIAZ （17.5 ±8.9）% group were significandy lower than those in RPC ＋5-HD （46.1 ± 10. 1）% and DMSO （36.4 ± 10.9） % group （P 〈 0.01 ）. There was no statistical difference in the infarct volume percentage between DMSO group RPC ＋ 5-HD group （ P = 0. 216） and between DIAZ group and RPC ＋ NS group （ P = 0.747 ）. CONCLUSION ： The blocking of mitochondrial ATP-sensitive potassium channel can abolish the neuroprotective effect induced by RPC in rat. It suggests that ischemic tolerance induced by RPC is dependent on the activation of mitochondrial ATP-sensitive potassium channel.

关 键 词：远程预处理 线粒体敏感性钾离子通道 脑缺血 再灌注 

分 类 号：R743.31[医药卫生—神经病学与精神病学]