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作 者:杨菁[1] 石海燕[1] 李莹[1] 王洪新[2] 金英[2] 刘春娜[2]
机构地区:[1]辽宁医学院细胞生物学及新药开发重点实验室,辽宁锦州121001 [2]辽宁医学院药理学教研室,辽宁锦州121001
出 处:《中国药理学与毒理学杂志》2008年第3期165-169,共5页Chinese Journal of Pharmacology and Toxicology
基 金:辽宁省高校分子细胞生物学与新药开发重点实验室开放课题(2006LY07);辽宁省教育厅资助课题(20060528)~~
摘 要:目的研究地黄寡糖对脑缺血再灌注致痴呆大鼠学习记忆功能的影响及其可能机制。方法采用ip硝普钠及双侧颈总动脉夹闭10min-再灌10min-夹闭10min的方式制备脑损伤模型。地黄寡糖6.4,32.0或160.0mg.kg-1于造模前3d至造模后7dip给药,每日1次,共10d。于术后d7开始进行水迷宫实验测定大鼠学习记忆能力;术后d10取海马,HPLC异硫氰酸苯酯柱前衍生法测定海马谷氨酸(Glu)含量;Western蛋白印迹法测定海马磷酸化细胞外信号调节激酶2(p-ERK2)含量。结果模型组大鼠学习记忆能力明显下降,海马Glu含量明显升高,p-ERK2含量降低。地黄寡糖可剂量依赖性地增强缺血再灌注损伤大鼠的学习记忆能力,降低海马Glu含量,提高海马p-ERK2含量。结论地黄寡糖可以改善脑缺血再灌注致痴呆大鼠的学习记忆能力,这种作用可能与抑制Glu过量释放、进而使ERK2信号途径正常发挥有关。AIM To investigate the effect of Rehmannia glutinosa oligosaccharides ( ROS ) on learning and memory abilities in rats with focal cerebral ischemia-reperfusion injury and its possible mechanism. METHODS Rat model of ischemia-reperfusion injury was established by 10 min ischemia-10 min reperfusion-10 min ischemia (I-R-I) of bilateral common carotid arteries and pretreated (ip) with sodium nitroprusside 2.5 mg· kg^-1 The rats were given (ip) ROS (6.4, 32.0 or 160.0 mg·kg^-1) once daily for 10 d (from 3 d prior to 7 d after I-R-I). On d 7 -9 after I-R-I, learning and memory abilities of rats were tested by Morris water maze. On d 10 after I-R-I, hippocampal glutamate (Glu) content and hippocampal phospho-extracellular signal regulated kinase 2 (p-ERK2) expression were detected by HPLC and Western blot, respectively, after finishing Morris water maze test. RESULTS Compared with the sham group, learning and memory abilities of model group were decreased, hipp-ocampal Glu content was increased, and hipp- ocampal p-ERK2 expression was decreased significantly. ROS treatment significantly improved the learning and memory abilities of rat with I-R-I injury, decreased hippocampal Glu content, and increased hippocampal p-ERK2 expression. CONCLUSION ROS can improve learning and memory abilities of rats with I-R-I injury, which may be related with inhibiting the elevation of hippocampal Glu content and sustain the ERK2 signaling pathways.
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