丙泊酚后处理对脑缺血-再灌注大鼠ADAR2-AMPA受体GluR2通路的作用  

Effect of propofol post-conditioning on ADAR2-AMPA receptor GluR2 pathway in a rat model of focal cerebral ischemia-reperfusion injury

作　　者：朱敏[1] 傅巍[1] 王海云[1] 王国林[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

出　　处：《临床麻醉学杂志》2015年第7期693-696,共4页Journal of Clinical Anesthesiology

基　　金：国家自然科学基金资助项目(81071059;81100984;81371245);天津市卫生局科技基金(09KZ106)

摘　　要：目的 研究丙泊酚后处理对脑缺血-再灌注大鼠腺苷脱氨酶（adenosine deaminase acting on RNA2,ADAR2）-α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid,AMPA）受体GluR2亚基（ADAR2-AMPA受体GluR2）通路的作用。方法 健康雄性SD大鼠120只,体重260-280g,采用随机数字表法均分为三组：假手术组（S组）、缺血-再灌注组（IR组）和丙泊酚后处理组（P组）。IR组和P组采用大脑中动脉阻塞1h的方法制备大鼠脑缺血-再灌注损伤模型,P组于再灌注即刻经股静脉输注20mg·kg^-1·h^-1丙泊酚2h,S组和IR组给予等容量生理盐水。于处理后24h行改良神经行为学评分（mNSS）;2,3,5-氯化三苯基四氮唑染色（TTC）测定脑梗死体积;RT-PCR检测缺血侧海马ADAR2mRNA表达;Western blot法检测缺血侧海马ADAR2胞核及总蛋白表达;巢式RT-PCR和特异性限制性内切酶BbV1检测ADAR2受体GluR2mRNA Q/R位点编辑比例。结果 三组ADAR2mRNA和总蛋白表达差异无统计学意义。与S组比较,IR组和P组mNSS评分明显升高,脑梗死体积明显增加,ADAR2胞核/总蛋白表达比例明显降低,GluR2mRNA Q/R位点编辑比例明显下降（P〈0.05）;与IR组比较,P组mNSS评分明显降低,脑梗死体积明显减少,ADAR2胞核/总蛋白表达比例明显增加,GluR2mRNA Q/R位点编辑比例明显升高（P〈0.05）。结论 丙泊酚后处理对脑缺血-再灌注大鼠有急性脑保护作用,该作用可能与丙泊酚促进ADAR2蛋白核转位,进而增加AMPA受体GluR2亚基mRNA编辑有关。Objective To investigate the effect of propofol post-conditioning on adenosine deaminase acting on RNA2（ADAR2）-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid（AMPA）receptor GluR2 subunit pathway in a rat model of focal cerebral ischemia-reperfusion injury.Methods One hundred and twenty male Sprague-Dawley rats,weighing 260-280 g,were randomly divided into 3groups（n=40）：sham operation group（group S）,ischemia and reperfusion group（group IR）and propofol post-conditioning group（group P）.The model of focal cerebral I/R injury was established by middle cerebral artery occlusion for 1hin group IR and group P.Rat from group P was infused by propofol 20mg·kg-1·h-1 over 2hstarting from the onset of reperfusion.The equal volume of normal saline was given in group IR and group S.After 24 h,the modified Neurological Severity Score（mNSS）was applied for assessing the rats＇ neurological function.The cerebral infarct volume was detected by TTC staining.The expression of ADAR2 protein was analyzed by Western blotting.Reverse transcription PCR（RT-PCR）was performed for determination of ADAR2 mRNA.The ratio of GluR2 mRNA Q/R edited was analyzed by Nest RT-PCR and BbV1.Results There was no statistical differences about the expression of ADAR2 mRNA and total protein among three groups.Compared with group S,there are statistically decreased in ratios of ADAR2nuclear/total protein and the ratio of GluR2 mRNA Q/R edited/total;significantly increased in the cerebral infarct volume and the mNSS in groups IR and P（P〈0.05）.However compared with group IR,propofol post-conditioning statistically increased ratios of ADAR2nuclear/total protein and the ratio of GluR2 mRNA Q/R edited/total;significantly decreased in the cerebral infarct volume and the mNSS（P〈0.05）.Conclusion Propofol post-conditioning could provide neuroprotection in a rat of model of focal cerebral ischemia-reperfusion injury,which maybe related to promote nuclear translocation of ADAR2 and increase the edited ratio of AMPA r

关 键 词：丙泊酚 后处理 腺苷脱氨酶 再灌注损伤 脑保护 

分 类 号：R614[医药卫生—麻醉学]