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中国应用生理学杂志 ›› 2020, Vol. 36 ›› Issue (2): 138-142.doi: 10.12047/j.cjap.5902.2020.031

• 研究论文 • 上一篇    下一篇

丁苯酞对慢性酒精中毒大鼠海马、杏仁核H2S/CBS通路及学习记忆能力的影响*

姚良雪1, 韩家鑫1, 魏培韵1, 侯思博1, 何潇剑1, 张瑞岭1,2△, 杜爱林1,2△   

  1. 1.新乡医学院生理学与神经生物学教研室, 中英脑功能损伤联合实验室, 河南省高校脑研究重点实验室培育基地 河南 新乡 453003;
    2.新乡医学院第二附属医院, 河南省生物精神病学重点实验室, 河南 新乡 453003
  • 出版日期:2020-03-28 发布日期:2020-07-31
  • 通讯作者: Tel: 13462256118; E-mail: duailin@126.com, zhangruilingxx@163.com
  • 基金资助:
    *国家自然科学基金联合基金项目(U1804170);河南省医学教育研究课题(Wjlx2018104);新乡医学院研究项目(2019-XYJG-84);河南省教育厅课题(15A310006);河南省卫生计生科技创新型人才“51282”工程;新乡医学院博士启动项目共同资助

Effects of butylphthalide on H2S/CBS pathway in hippocampal and amygdala and learning and memory ability in chronic alcoholism rats

YAO Liang-xue1, HAN Jia-xin1, WEI Pei-yun1, HOU Si-bo1, HE Xiao-jian1, ZHANG Rui-ling1,2△, DU Ai-lin1,2△   

  1. 1. Department of Physiology and Neurobiology, Sino-UK Joint Laboratory for Brain Function and Injury, Henan Provincial Key Laboratory of Brain Research, Xinxiang 453003;
    2. The Second Affiliated Hospital of Xinxiang Medical University, Henan Key Laboratory of Biopsychology, Xinxiang Medical University, Xinxiang 453003, China
  • Online:2020-03-28 Published:2020-07-31

摘要: 目的: 探讨丁苯酞(NBP)对慢性酒精中毒大鼠学习与记忆相关的能力、海马及杏仁核内硫化氢(H2S)含量、胱硫醚-β-合成酶(CBS)表达和线粒体ATP酶活性的影响。方法: 随机将90只SD雄性大鼠均分为3组:空白对照组(NC)、模型组(M)和治疗组。除对照组外,其余两组均将含6%(v/v)酒精的水溶液作为唯一饮水来源。喂养14d后,治疗组按5mg/Kg比例腹腔注射NBP,每日一次,连续14d,其余两组注射等剂量生理盐水;对照组随后使用Morris水迷宫法,通过观察和记录动物入水后搜索藏在水下平台所需时间、采用策略和它们的游泳轨迹,从而可分析和推断动物的学习、记忆等方面的能力,并检测海马和杏仁核组织中H2S浓度、CBS表达及线粒体ATP酶活性。结果: 与正常对照组大鼠相比,模型组大鼠第2-4日潜伏期、游泳距离均增加,海马及杏仁核内H2S含量、CBS平均光密度值均升高,海马以及杏仁核组织中线粒体ATP酶活性均降低,且均有极显著性差异(P<0.01)。与模型组大鼠相比较,NBP治疗组大鼠学习记忆成绩第2-4日潜伏期、游泳距离减小,海马及杏仁核H2S含量、CBS平均光密度值均降低,海马以及杏仁核组织中线粒体ATP酶活性均提高,且均有极显著性差异(P<0.01)。结论: NBP能够减轻酒精对大鼠的学习与记忆能力的影响,可能与NBP影响海马、杏仁核内H2S浓度和CBS的表达以及线粒体ATP酶活性有关。

关键词: 丁苯酞, 慢性酒精中毒, 大鼠, 学习记忆能力, 海马, 杏仁核, H2S/CBS

Abstract: Objective: To investigate the effects of butylphthalide (NBP) on learning and memory related ability, hydrogen sulfide (H2S) content in hippocampus and amygdala, cystathionine-β-synthase (CBS) expression and mitochondrial ATPase activity in rats with chronic alcoholism. Methods: Ninety SD male rats were randomly divided into three groups: normal control group (NC), model group (M) and butylphthalide remedy group (BR). Except for the control group, the water solution containing 6% (v/v) alcohol was used as the sole source of drinking water in the other two groups. After 14 days of feeding, the butylphthalide remedy group was injected with NBP intraperitoneally at the dose of 5 mg/kg once a day for 14 consecutive days, and the remaining two groups were injected with the same dose of normal saline. The control group subsequently used the Morris water maze method to observe and record the animals after entering the water. The time required for the underwater platform, their strategies and their swimming trajectories could analyze and infer the animal's ability to learn and remember. H2S concentration, CBS expression and mitochondrial ATPase activity in hippocampus and amygdale were dectected. Results: Compared with NC group, the latency period and swimming distance of M group were increased, the content of H2S and the mean optical density of CBS in hippocampus and amygdala were increased, and the activity of mitochondrial ATPase in hippocampus and amygdala was decreased significantly (P<0. 01) . Compared with the M group, the latency period and swimming distance of learning and memory performance of BR group were decreased, the content of H2S and the mean optical density of CBS in hippocampus and amygdala were decreased, and the activity of mitochondrial ATPase in hippocampus and amygdala was increased significantly (P<0. 01) . Conclusion: NBP can alleviate the effect of ethanol on learning and memory in rats, which may be related to the effect of NBP on the concentration of H2S and the expression of CBS in the amygdala of hippocampus and the increase of ATPase activity.

Key words: butylphthalide, chronic alcoholism, rats, learning and memory ability, hippocampal, amygdala, H2S/CBS

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