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机构地区:[1]徐州医学院药理学教研室 [2]山东枣庄市立医院药剂科
出 处:《中国临床药理学与治疗学》2011年第5期488-491,共4页Chinese Journal of Clinical Pharmacology and Therapeutics
摘 要:目的:研究磷酸化环磷酸腺苷反应蛋白结合元件(p-CREB)在激动γ-羟基西酸(GHB)受体对大鼠局灶性脑缺血再灌注损伤的保护作用中的变化。方法:SD大鼠随机分为Sham组,I/R组,NCS-356 160、320、640μg/kg组。采用改良的Longa线栓法缺血2 h/再灌2 h建立I/R模型。分别于缺血前30 min和再灌前icv给予药物;5分制评分法评价大鼠神经功能。再灌24 h后免疫组织化学法测定p-CREB的表达。结果:I/R组大鼠行为学评分为3.2±0.7,明显高于Sham组(n=8,P<0.01);NCS-356 640μg/kg组的行为学评分则明显低于I/R组(n=8,P<0.05)。I/R组大鼠缺血区脑皮层细胞核内p-CREB的表达为96.3±6.0,明显高于Sham组(n=8,P<0.01);NCS-356 320μg/kg组和NCS-356640μg/kg组脑缺血皮层细胞核内p-CREB的表达与I/R组比较明显降低(n=8,P<0.01)。结论:激动GHB受体对大鼠局灶性脑缺血再灌注损伤具有一定的保护作用,且缺血组织p-CREB的表达在此保护作用中降低。AIM: To investigate the change of p-CREB in the protection effect of agitating gamma-hydroxybutyric acid receptor on focal cerebral ischemia-reperfusion injury in rats. METHODS: The Sprague-Dawley rats were randomly divided into five groups: sham operation group(Sham),ischemia-reperfusion group(I/R),NCS-356 160,320,640 μg/kg group.The middle cerebral artery occlusion(MCAO) model referring to Longa's method with modifications was adopted.These groups were administered NCS-356 in right lateral cerebral ventricle.Behavioral consequence of MCAO rats was studied 2 h after ischemia reperfusion.After 24 h of ischemia reperfusion,rats' ischemic cortex were used to measure the phosphorylation cAMP reactive protein binding element(p-CREB) by immunohistochemical method.RESULTS:The ethology score in rats of I/R group was 3.2±0.7,compared with the Sham group,it was increased statistically(n=8,P〈0.01) The neurological function score in NCS 640 group was obviously lower than that in I/R group(n=8,P〈0.05).The p-CREB gray scale value in I/R group was 96.3±6.0,which was higher than that in Sham group(n=8,P〈0.01).The p-CREB gray scale value in NCS 640 group and NCS 320 group was obviously lower than that in I/R group(n=8,P〈0.01).CONCLUSION: Activating GHBR has protective effects on focal cerebral ischemia-reperfusion injury in rats.The expresstion of p-CREB is reduced in the protection effect of agitating gamma-hydroxybutyric acid receptor on focal cerebral ischemia-reperfusion injury in rats.
关 键 词:Γ-羟基丁酸受体 大鼠 脑缺血再灌注 磷酸化环磷酸腺苷反应蛋白结合元件
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