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梓醇上调GAP-43表达伴随局灶脑缺血大鼠神经功能恢复 被引量:36

Catalpol up-regulated GAP-43 protein expression and improved behavior outcome of focal cerebral ischemia rats
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摘要 目的观察滋阴中药地黄的主要活性成分梓醇对局灶脑缺血大鼠神经功能恢复及缺血周围区大脑皮质生长相关蛋白-43表达的影响。方法♂SD大鼠42只,随机分为假手术组、模型组、生理盐水组、梓醇低、中、高剂量治疗组(剂量分别为1、5、10mg.kg-1)和胞二磷胆碱(剂量为0.4g.kg-1)对照组,每组6只。采用开颅电凝右侧大脑中动脉的方法制备局灶脑缺血模型。造模后6h,经腹腔注射首次给予梓醇进行干预,每天1次,连续7d。给药前及术后1、4、7及15d分别评定各组大鼠姿势反射及肌力变化,并在术后15d断头取脑,制备脑片和脑组织匀浆,采用免疫荧光组织化学染色和Western blot检测缺血周围区大脑皮质GAP-43蛋白表达。结果假手术组无明显神经功能障碍;梓醇高、中剂量治疗组姿势反射及肌力恢复明显优于模型组、生理盐水组和胞二磷胆碱组,且梓醇各剂量治疗组缺血周围区GAP-43蛋白表达比其它实验组明显上调(P<0.05)。结论梓醇可上调脑缺血大鼠缺血周围区皮质GAP-43表达,促进轴突再生,加速其神经功能恢复。 Aim To investigate the effects of catalpol from Radix Rehmanniae on behavior outcome of rats with focal cerebral ischemia and the expression patterns of growth-associated protein-43(GAP-43)in the cerebral cortex surrounding the ischemic core.Methods 42 adult male Sprague-Dawley rats were randomized into 7 groups,including sham operation group,model group,normal saline control group,low dose,middle dose and high dose of catalpol treatment group(1,5 and 10 mg.kg^-1,ip,respectively) and citicoline treatment control group(0.4 mg.kg^-1,ip).A small craniectomy was performed from the posterior zygoma and along the temporal ridge of the cranium extending ventrally to expose the right middle cerebral artery(MCA) and olfactory tract.The base of MCA was electrico-coagulated,and the permanent focal cerebral ischemia animal model was established.Animals were assigned to receive intraperitoneally either different does of catalpol treatment or citicoline treatment,once a day for 7 successive days,and the first dose was given at the time point of 6h post-operation.Attitudinal reflexes and muscle strength were assessed just before the first dose was given and 1,4,7 d and 15 d time points after operation.After 15 days of behavioral testing,animals were deeply anesthetized and then sacrificed.Brain tissue was removed as quickly as possible,and brain sections and brain tissue homogenate were prepared for studying the expression patterns of growth-associated protein-43 in the cerebral cortex surrounding the ischemic core using immunofluorescence histochemistry and Western blot.Results Compared with the model group,in the normal saline control group and the citicoline control group,attitudinal reflexes and muscle strength in high dose and middle dose of catalpol treatment groups(10 and 5 mg.kg^-1,respectively) were ameliorated significantly,and there was no obvious dysfunction in the sham group;the protein expression of GAP-43 in the model rats of the catalpol treatment group(1,5 and 10 mg.kg^-1) increased sign
出处 《中国药理学通报》 CAS CSCD 北大核心 2007年第9期1231-1236,共6页 Chinese Pharmacological Bulletin
基金 国家自然科学基金资助项目(No30070915 30470606) 重庆市科委应用基础项目(渝科发计字[2002]18-99 渝科计[2002]18-93) 重庆市卫生局中医药科研计划项目(渝中医[2002]42-30) 重庆市科委攻关项目(渝科计[2003]43-6)
关键词 梓醇 脑缺血 神经可塑性 生长相关蛋白-43 catalpol cerebral ischemia neural plasticity growth-associated protein-43
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