天津医药

天津医药 ›› 2019, Vol. 47 ›› Issue (4): 391-394.doi: 10.11958/20181474

• 实验研究 • 上一篇    下一篇

木兰花碱减轻慢性应激小鼠抑郁样行为及对脑部LSD1组蛋白修饰的影响

曹冰雁 1，刘艺洁 2，武莉莉 2，费乔曼 2，杨冰 2，张玲 2，乔卫 1△   

  1. 1天津医科大学药学院，天津市临床药物关键技术重点实验室（邮编 300070）；2天津医科大学基础医学院
  • 收稿日期:2018-09-26 修回日期:2019-03-22 出版日期:2019-04-15 发布日期:2019-05-27
  • 通讯作者: 乔卫 E-mail:qiaowei@tmu.edu.cn
  • 作者简介:曹冰雁（1996），女，硕士在读，主要从事中药药理学与分子生物学相关研究
  • 基金资助:
    国家自然科学基金资助项目;天津市自然科学基金重点项目

The effects of magnoflorine on depression-like behavior in chronic unpredictable mild stress mice and its effect on LSD1 modification in brain

CAO Bing-yan1, LIU Yi-jie2, WU Li-li2, FEI Qiao-man2, YANG Bing2, ZHANG Ling2, QIAO Wei1△   

  1. 1 School of Pharmacy, Tianjin Medical University, Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Tianjin 300070, China; 2 School of Basic Medical Sciences, Tianjin Medical University
  • Received:2018-09-26 Revised:2019-03-22 Published:2019-04-15 Online:2019-05-27

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摘要： 目的 探索木兰花碱对慢性不可预见性温和应激所致抑郁小鼠行为学的影响机制。方法 将 ICR小鼠随 机分为正常对照组（control组）、抑郁模型组（PG组）、木兰花碱高剂量组（MH组）和木兰花碱低剂量组（ML组）。采用 慢性不可预见性温和刺激方法建立抑郁小鼠模型，检测各组小鼠行为学的变化，并用实时定量 PCR、Western blot检 测小鼠脑部赖氨酸特异性组蛋白去甲基化酶 1（LSD1）mRNA及蛋白表达水平的变化。免疫组化染色法检测小鼠脑 部 LSD1阳性细胞数量。结果 木兰花碱在行为学上改善了小鼠的抑郁状况，与 PG组相比，MH组和 ML组悬尾不动 时间、强迫游泳不动时间明显缩短（P＜0.05）。实时定量 PCR及 Western blot结果显示，与 control组相比，PG组 LSD1 mRNA表达差异无统计学意义，蛋白表达明显降低（P＜0.05），ML组 LSD1 mRNA和蛋白表达明显升高（P＜0.05）；与 PG组相比，ML组 LSD1 mRNA和蛋白表达明显升高（P＜0.05）。免疫组化结果显示，与 control组相比，PG组小鼠脑部 LSD1阳性细胞数量减少，而 ML组较 PG组增加。结论 在木兰花碱治疗抑郁小鼠的过程中，LSD1可能起到了重要 的调节作用。

关键词: 抑郁, 慢性不可预见性温和刺激, 木兰花碱, 赖氨酸特异性组蛋白去甲基化酶 1

Abstract: Objective To explore the mechanism of the effect of magnoflorine on the behavior of mice with depression caused by chronic unpredictable mild stress. Methods The ICR mice were randomly divided into normal control group (control group), positive depression group (PG group), high dose of magnoflorine group (MH group) and low dose of magnoflorine group (ML group). Depression mouse model was established by chronic unpredictable mild stress method. The behavioral changes of mice were detected. The expressions of lysine specific demethylase 1 (LSD1) mRNA and protein in brain of mice were detected by real-time quantitative PCR, Western blot assay and immunohistochemistry. Results Magnoflorine improved the depression in mice. Compared with the PG group, the motionless time of tail suspension and motionless time of forced swimming were significantly shorter in the MH group and the ML group (P＜0.05). Real-time quantitative PCR and Western blot assay showed that there was no significant difference in LSD1 mRNA expression between the PG group and the control group. The protein expression was significantly decreased (P＜0.05). The expressions of LSD1 mRNA and protein were significantly increased in the ML group compared with those of control group (P＜0.05). Compared with the PG group, the expressions of LSD1 mRNA and protein were significantly increased in the ML group (P＜0.05). The results of immunohistochemistry showed that the number of positive cells in brain was decreased in the PG group compared with that of the control group, while it was increased in the ML group compared with that of PG group. Conclusion LSD1 may play an important role in the treatment with magnoflorine for depressed mice.

Key words: depression, chronic unpredictable mild stress, magnoflorine, lysine specific demethylase 1