丁苯酞通过调节海马突触相关蛋白表达和线粒体结构改善 db / db 小鼠认知功能障碍
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中国医学科学院医学实验动物研究所,北京协和医学院比较医学中心,北京 100021

中图分类号:

R-33


N-butylphthalide ameliorates cognitive dysfunction in db / db mice by regulating hippocampal synapse-associated protein expression and mitochondrial structure
Author:
Affiliation:

Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences; Comparative Medical Center, Peking Union Medical College, Beijing 100021, China

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    摘要:

    目的 观察不同剂量丁苯酞(N-butylphthalide,NBP) 对 db / db 小鼠认知功能及海马区突触素 (synaptophysin,SYN)、突触后致密物 95(postsynaptic density-95 protein,PSD-95)的表达以及线粒体结构的影响。 方法 实验共分 5 组,将 20 只 db / db 小鼠随机分 4 组,模型组、低、中、高剂量治疗组,每组 5 只,同窝正常 db / m 小鼠 5 只作为对照组。 在 6 周龄时,分别给予 db / db 小鼠腹腔注射低、中、高剂量(20、40、60 mg / kg)的丁苯酞注射液,对照组和模型组均给予等体积的生理盐水腹腔注射,每日 1 次,连续 6 周。 每周监测体重与空腹血糖水平,运用 Morris 水迷宫实验检测小鼠的空间学习记忆能力,Western blot 技术检测小鼠海马区 SYN、PSD-95 表达,电镜观察海马区线粒体的结构。 结果 与模型组相比,各治疗组对小鼠的体重及血糖影响无显著差异,但水迷宫探索期逃避潜伏时间减少(P<0. 05),测试期跨越平台次数增加(P<0. 01),海马区 SYN、PSD-95 蛋白表达量均升高(P<0. 05), 且认知改善和蛋白表达增加呈剂量依赖关系;电镜下正常组的线粒体结构正常,嵴结构清晰并且排列紧密,膜结构完整;模型组线粒体受损,嵴结构稀疏,融合,逐渐空泡化;各剂量治疗组海马区线粒体大部分结构完整,嵴结构有少量破坏,膜结构也相对完整。 结论 丁苯酞可能通过调节海马突触相关蛋白 SYN、PSD-95 的表达和线粒体结构改善 db / db 小鼠的认知功能障碍,高剂量治疗效果优于低剂量与中剂量组。

    Abstract:

    Objective In this study, we aimed to investigate the effects of different doses of n-butylphthalide (NBP) on cognitive function in db / db mice, the expression of synaptophysin (SYN) and post-synaptic density-95 (PSD- 95) proteins in the hippocampus, as well as mitochondrial structure in the hippocampus. Methods A total of 20 db / db mice were randomly divided into four groups: model group, and low, medium and high-dose treatment groups (five mice in each group). In addition, five normal db / m mice from the same litter were used as the control group. At the age of 6 weeks, db / db mice in the low, medium and high-dose groups were intraperitoneally injected with NBP at a concentration of 20, 40 and 60 mg / kg, respectively, while the control group and the model group were given the same volume of normal saline. Injections were given once a day for 6 weeks. Body weight and fasting blood glucose level were monitored weekly. Morris water maze was used to assess spatial learning and memory abilities. Western blot was used to detect the expression of SYN and PSD-95 in the hippocampus, and the structure of hippocampal mitochondria was observed by electron microscopy. Results Compared with the model group, there was no significant difference in body weight or blood glucose in any treatment group. However, during the water maze exploration period, escape latency was reduced (P< 0. 05), the number of platform crossings was increased (P< 0. 01), protein expression levels of SYN and PSD-95 in the hippocampus were increased (P< 0. 05), and there was a positive relationship between cognitive improvement and protein expression. Under the electron microscope, mitochondrial structure in the control group was normal, the ridge structure was clear and tightly arranged, and the membrane structure was intact. In the model group, mitochondria were damaged, and cristae were sparse, fused and vacuolated. In the treatment groups, most of the mitochondria in the hippocampus were intact, while cristae structure was slightly perturbed, and membrane structure was relatively intact. Conclusions NBP alleviates cognitive dysfunction in db / db mice by regulating the expression of the hippocampal synaptic proteins SYN and PSD-95, and by improving mitochondrial structure. The therapeutic effect in the high dose group was better than that in the low and medium-dose groups.

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左旺盛,张 钰,张 玲,秦 川.丁苯酞通过调节海马突触相关蛋白表达和线粒体结构改善 db / db 小鼠认知功能障碍[J].中国比较医学杂志,2021,31(4):27~32.

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  • 收稿日期:2020-12-27
  • 在线发布日期: 2021-05-28
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