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作 者:张雪[1] 黄仕营[1] 张燊[2] 丁秀芳[1] 陈宝田[1]
机构地区:[1]南方医科大学南方医院中医科,广东广州510515 [2]南方医科大学研究生学院,广东广州510515
出 处:《南方医科大学学报》2012年第1期80-84,共5页Journal of Southern Medical University
基 金:广东省211工程三期重点学科项目(粤2009431)
摘 要:目的观察安神方颗粒的抗焦虑作用,并研究其机制。方法 60只雄性Wistar大鼠随机分为6组(10只/组):正常对照组、模型组、地西泮组和安神方高、中、低剂量组。采用慢性情绪应激的方法建立焦虑大鼠模型,同时给予药物干预,以高架十字迷宫试验对其行为学进行评价。行为学观察后,麻醉处死正常对照组、模型组、地西泮组及安神方中剂量组大鼠,冰台上分离大鼠海马,冷冻离心后分离上清液,高效液相色谱法测定谷氨酸、γ-氨基丁酸(GABA)含量;用免疫组织化学法测定γ-氨基丁酸受体(GABAAR)、N-甲基-D-天冬氨酸受体1(NMDAR1)的表达。结果与正常对照组比较,模型组大鼠进入开臂的时间百分率、次数百分率明显减少;地西泮组与安神方高、中、低剂量组大鼠进入开臂的时间百分率、次数百分率较模型组显著上升,以安神方中剂量组上升最明显;模型组大鼠海马组织中谷氨酸的表达量较正常对照组显著上升,GABA的表达量明显下降;地西泮组和安神方中剂量组同模型组比较,大鼠海马组织中谷氨酸的表达量显著降低和GABA的表达量明显提高,安神方中剂量组与地西泮组比较差异不显著;模型组与正常对照组比较,GABAAR免疫阳性细胞表达减少,NMDAR1免疫阳性细胞表达表达增多;地西泮组和安神方中剂量组同模型组比较,NMDAR1的表达水平降低,GABAAR的表达水平提高,安神方中剂量组与地西泮组比较无明显差异。结论安神方具有抗焦虑的作用,可以提高中枢GABA的含量,增强GABAAR的表达,降低谷氨酸含量,减少NMDAR1的表达。Objective To assess the anxiolytic effect of Anshenfang granules(ASF),a compound traditional Chinese medicinal preparation,on anxiety in rats and the mechanism of its actions.Methods Male Wistar rats with anxiety induced by chronic emotional stress were randomized to receive treatments with diazepam or ASF at high,medium or low doses.The behavioral changes of the rats were evaluated using plus-maze test,after which the rats in normal control group,model group,and medium AFS dose group were sacrificed to measure the hippocampal contents of glutamic acid and γ-aminobutyric acid(GABA) using high-performance liquid chromatography(HPLC);immunohistochemistry was employed to evaluate the expressions of GABAA receptor and N-methyl-D-aspartate receptor 1(NMDAR1).Results Plus-maze test showed obvious anxiety behaviors in the model group,which were significantly meliorated by diazepam and ASF,especially at the medium dose.Hippocampal glutamate levels increased and GABA decreased significantly in the model group,and such changes were obviously attenuated,by comparable amplitudes,by treatments with diazepam and medium-dose ASF.The model group showed significantly diminished GABAA receptor-positive cells and increased NMDAR1-positive cells,which were improved by diazepam and ASF at the medium dose.Conclusion ASF produces strong anxiolytic effect in rats by increasing the content of GABA in the brain,enhancing GABAA receptor expression,reducing glutamic acid content,and decreasing NMDAR1 expression.
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