异丙酚后处理对大鼠脑缺血再灌注损伤时含GluR1亚基AMPA受体表达的影响  

Effect of propofol post-conditioning on expression of GluR1-containing AMPA receptors during cerebral ischemia-reperfusion injury in rats

作　　者：王斌[1] 王国林[1] 陈骏[2] 王海云[1] 

机构地区：[1]天津医科大学总医院麻醉科天津市麻醉学研究所,300052 [2]天津医科大学基础医学院微生物教研室

出　　处：《中华麻醉学杂志》2015年第2期204-207,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81071059,81100984,81371245）

摘　　要：目的 评价异丙酚后处理对大鼠脑缺血再灌注损伤时含GluR1亚基AMPA受体表达的影响.方法 选取健康雄性SD大鼠46只,体重250～280 g,7～8周龄,采用随机数字表法,将其分为3组（n=18）：假手术组（S组）、缺血再灌注组（I/R组）、异丙酚组（P组）.I/R组和P组采用线栓法阻塞大脑中动脉1h后恢复灌注,制备局灶性脑缺血再灌注损伤模型.P组于再灌注即刻开始静脉输注异丙酚20 mg·kg^-1·h^-1 2 h,S组、I/R组以等容量生理盐水替代.于术后7、14、28 d时行恐惧条件化实验,记录场景相关僵直时间和条件诱导僵直时间,计算僵直时间百分比;于再灌注24 h时行改良神经功能缺陷评分,测定脑梗死体积百分比;取海马组织,测定蛋白激酶A（PKA）、A型锚定蛋白（AKAP） 150、AMPA受体GluR1亚基及其第845位点丝氨酸（Ser845）磷酸化水平.结果 与S组比较,I/R组与P组改良神经功能缺陷评分和脑梗死体积百分比升高,海马PKA、pGluR1 Ser845表达下调,术后7、14 d时场景相关僵直时间百分比和条件诱导僵直时间百分比降低（P＜0.05）.与I/R组比较,P组改良神经功能缺陷评分和脑梗死体积百分比降低,海马PKA、pGluR1 Ser845表达上调,术后7、14 d时场景相关僵直时间百分比和条件诱导僵直时间百分比升高（P＜0.05）.结论 异丙酚后处理减轻大鼠脑缺血再灌注损伤的机制与AMPA受体GluR1亚基磷酸化有关.Objective To evaluate the effect of propofol post-conditioning on the expression of GluR1-containing AMPA receptors during cerebral ischemia-reperfusion （I/R） injury in rats.Methods Sixtyfour healthy male Sprague-Dawley rats,aged 7-8 weeks,weighing 250-280 g,were randomly divided into 3 groups （n =18 each） using a random number table：sham operation group （group S）,I/R group and propofol group （group P）.Focal cerebral ischemia was induced by occlusion of the middle cerebral artery for 1 h followed by reperfusion in I/R and P groups.Propofol was infused at 20 mg · kg^-1 · h^-1 for 2 h starting from the onset of reperfusion in group P,and the equal volume of normal saline was given in S and I/R groups.Fear conditioning test was performed on 7,14 and 28 days after operation.The time spent freezing induced by context and condition was recorded,and the percentage was calculated.The modified neurological deficit score （NDS） was measured at 24 h of infusion.The cerebral infarct size was measured by TTC.The hippocampal samples were isolated for determination of the expression of protein kinase A （PKA）,A-kinase anchoring protein 150 （AKAP150） and AMPA receptor GluR1 subunit and phosphorylation of GluR1 at serine 845 （Ser845） site （pGluR1 Ser845）.Results Compared with group S,the NDS and cerebral infarct size were significantly increased,the expression of PKA and pGluR1 Ser845 was down-regulated,and the percentage of time spent freezing induced by context and condition was decreased on 7 and 14 days after operation in I/R and P groups.Compared with group I/R,the NDS and cerebral infarct size were significantly decreased,the expression of PKA and pGluR1 Ser845 was upregulated,and the percentage of time spent freezing induced by context and condition was increased on 7 and 14 days after operation in group P.Conclusion The mechanism by which propofol postconditioning reduces cerebral I/R injury is related to phosphorylation of AMPA receptor GluR1 subunit in rats.

关 键 词：二异丙酚 脑 再灌注损伤 受体 AMPA 

分 类 号：R614[医药卫生—麻醉学]