奥拉西坦/丁基苯酞对新生大鼠缺氧缺血性脑病的相关研究  

Early therapeutic effect of ORS /Butylphthalide on newborn rats with hypoxic-ischemic encephalopathy

作　　者：穆国军 李晓迪[1] 顾镜月[1] 李惠玲[1] 张伟东[1] 郭海涛[1] 

机构地区：[1]佳木斯大学附属第一医院儿内一科,黑龙江佳木斯154003

出　　处：《黑龙江医药科学》2014年第3期8-10,共3页Heilongjiang Medicine and Pharmacy

摘　　要：目的:研究联合应用奥拉西坦(ORS)和丁基苯酞(NBP)在新生大鼠缺氧缺血性脑病中的早期治疗作用。方法:出生7d大鼠共分为4组,每组25只。(1)空白组:分离左侧颈总动脉后在动脉下置线,不结扎亦不低氧。(2)模型组:制备大鼠缺血缺氧性脑病模型立即腹腔注射生理盐水0.1mL/只。(3)对照组:建模后立即腹腔注射ORS 100mg/kg。(4)实验组:造模成功后立即腹腔注射ORS 100mg/kg,30min后腹腔注射丁基苯酞10mg/kg。所有动物于注射药物后12h、24 h、3d、7d后断头处死取大脑组织,并对脑组织中含水量、SOD含量进行检测,通过免疫组化及western blot方法检测水通道蛋白-4(AQP-4)和环磷酸腺苷反应元件结合蛋白(CREB)的变化情况。结果:与模型组比较,实验组脑组织含水量明显低于对照组,但SOD结果显示高于对照组(P<0.05);通过免疫组化及western blot分析与模型组比较,可见AQP-4表达在对照组和实验组均有降低,但实验组低于对照组接近空白组,CREB蛋白在实验组中呈高表达接近空白组(P<0.05)。结论:大脑缺氧缺血后应用ORS/NBP可上调CREB蛋白并下调AQP-4,对新生大鼠缺氧缺血性脑病具有早期治疗作用。Objective： To study the early therapeutic effects of ORS combined with Butylphthalide in neonatal rats with hypoxic--ischemic encephalopathy. Methods： Seven days old rats were randomly divided into four groups （n= 25）, （1） blank group： healthy rats without the hypoxia treatment via setting the untied arterial lines after separation of the left common carotid artery; （2） model group： hypoxicischemic encephalopathy rat models injected with physiological saline solution of 0.1 mL per rat immediately via intraperitoneal injection; （3） control group： rat models injected with ORS of 1 mg/kg body weight immediately via intraperitoneal injection; （4） experimental group： rat models with ORS injected with Butylphthalide 100 mg/kg body weight at 30 rain post injection of ORS via the intraperitoneal. All animals at 12h, 1d,3d,and 7d post medicine injection were decapitated and the cerebral tissues were dissected. Water content and SOD activity in brain separately was detected. In addition, the water channel protein--4 （AQP--4） and the cyclic adenosine monophosphate response element binding protein （CREB） were analyzed on different gene expression patterns by immunohistochemistry and western blotting. Results： Compared with the model group, brain water content in the experimental group was significantly lower than that in the control group, but SOD showed higher than that in the control group （P 〈 0.05）. By immunohistochemistry and western blotting analysises, in the control group were reduced in comparsion with the model group. Moreover, the expression of AQP--4 in the experimental group was close to the blank group compared with the control group. CREB in the experimental group showed a high expression close to the blank control and experimental groups. Conclusion： The hypoxic--ischemic brain after administration of ORS/Butylphthalide can be induced to up--regulate CREB and downreg- ulate the expression of AQP--4, showing early treatment effects on neonatal rats with hypoxic

关 键 词：奥拉西坦 丁基苯酞 缺氧缺血性脑病 AQP-4 CREB蛋白 

分 类 号：R743[医药卫生—神经病学与精神病学]