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甘珀酸钠苦参素包合物对小鼠中枢的抑制作用

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目的:研究甘珀酸钠苦参素包合物(OCSIC)对小鼠中枢的抑制作用并探讨其机制.方法:采用行为药理学方法观察OCSIC对小鼠主动、被动活动协调能力及耐力对戊巴比妥钠(PENT)催眠作用的影响;γ-氨基丁酸(GABA)、地西泮(DZ)、3-哌啶甲酸乙酯(EN)的协同作用及对印防已毒素(PTX)、海人藻酸(KA)、N-methyl-D-aspartate(NMDA)所致惊厥的拮抗作用.采用免疫组织化学方法(SABC法)检测OCSIC对小鼠大脑皮层、海马GABA转运体1(GAT-1)蛋白表达的影响.结果:OCSIC 100,50,25 mg/kg分别使小鼠自主活动减少86.7%,85.6%,17.2%;PENT使入睡潜伏期分别缩短61.2%,49.0%,36.7%,而睡眠持续时间分别延长379.8%,146.2%,132.2%(P<0.01,P<0.05)并能明显加强阈下剂量PENT的催眠作用.阈下剂量的OCSIC与阈下剂量的GABA或EN合用分别可使小鼠自主活动率减少78.8%,47.0%(P<0.01);OCSIC 100 mg/kg与阈下抗惊厥剂量DZ(0.5 mg/kg)合用能对抗PTX致惊厥作用(P<0.05),但不能对抗KA,NMDA致惊厥作用.OCSIC能明显减少小鼠大脑皮层和海马GAT-1免疫阳性细胞的表达(P<0.01).结论:OCSIC具有中枢抑制作用,其作用机制与GABA神经功能有关.
Inhibitory effects of oxymatrine-carbenoxolonesodium inclusion complex on central nervous system in mice
AIM: To explore the influence of oxymatrine-carben-oxolone sodium inclusion complex ( OCSIC ) on the central nervous system. METHODS: The action of OCSIC on central nervous system was studied by observing the changes of initiative and passive activity's tolerance and harmonious motion,by measuring the influence of pentobarbital's hypnotic action,by coordinating with GABA,Diazepam or Ethylnipecotate and antagonizing the convulsion caused by Picrotoxin,Kainic acid and N-methyl-D-aspartate,and by adopting immunohistochemistry method ( SABC) to determine the gamma aminobutyric acid transporter-1 Protein (GAT-1) expression in the cerebral cortex and hippocampi in mice. RESULTS: Compared with those in control group,the spontaneous activity were reduced to 86. 7%,85. 6% and 17. 2% ( P < 0.01),the latent period of falling asleep induced by pentobarbital administration was shortened to 61. 2%,49. 0% and 36. 7% (P< 0. 01 ),the sustained period of sleep was lengthened to 379.8%,146.2% and 132.2% (P<0. 01,P<0.05),and the hypnotic action subsequent to the administration of pentobarbital in a subthreshold dose was greatly enhanced ( P < 0. 05) in mice treated intraperitoneally with respective OCSIC 100,50 or 25 mg/ kg in experimental group. OCSIC alone in a subthreshold dose reduced spontaneous activity to 78. 8% and combined administration with GABA or with Ethyl nipecotate in a subthreshold dose reduced spontaneous activity to 47. 0% (P < 0. 01 ). OCSIC 100 mg/kg with a subthreshold dose of anticonvulsion Diazepam (0.5 mg/kg) antagonized the convulsion caused by Picrotoxin ( P < 0.05),but not antagonize the convulsion caused by Kainic acid and N-methyl-D-aspartate. OCSIC decreased the number of GAT-1 in the cerebral cortex and hippocampi of mice ( P < 0. 01 ). CONCLUSION: OCSIC exerts inhibitory effects on the central nervous system,which may be related with GABA.

Oxymatrine-Carbenoxolone sodium Inclusion complexGABAsedationhypnoticaction

陶丽君、高进贤、金少举、余建强、郭凤英、周俊俊、蒋袁絮

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宁夏医科大学,药理学教研室,宁夏,银川,750004

宁夏医科大学,病理学教研室,宁夏,银川,750004

甘珀酸钠苦参素包合物 GABA 镇静 催眠

宁夏教育厅科研项目宁夏自然科学基金

2008293-39NZ0888

2009

第四军医大学学报
第四军医大学

第四军医大学学报

CSTPCDCSCD北大核心
影响因子:0.599
ISSN:1000-2790
年,卷(期):2009.30(9)
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