芍药苷对Bayk8644诱导大鼠抑郁焦虑样行为的改善作用及机制研究

doi:10.3969/j.issn.1674-5817.2020.06.005

实验动物与比较医学 ›› 2020, Vol. 40 ›› Issue (6): 489-495.DOI: 10.3969/j.issn.1674-5817.2020.06.005

• 实验动物与中医药专题 • 上一篇下一篇

芍药苷对Bayk8644诱导大鼠抑郁焦虑样行为的改善作用及机制研究

李萍¹, 李艺杰², 薛玲³, 宋春红³

1.青岛大学附属医院药学部,青岛 266001;
2.北京唯新唯实教育科技有限公司,北京102200;
3.山东中医药大学,教育部中医药经典理论研究重点实验室, 济南250355

收稿日期:2020-04-30 出版日期:2020-12-25 发布日期:2020-12-30
作者简介:李萍(1962-), 副主任药师, 从事中药药理研究。E-mail: liping_qy@126.com
基金资助:
国家自然科学青年基金(81403294), 国家重大新药创制项目子课题(2017ZX09301064005), 山东中医药大学SRT项目(2019041)

Effect and Mechanism of Paeoniflorin on Depression and Anxiety Behavior Induced by Bayk8644 in Rats

LI Ping¹, LI Yijie², XUE Ling³, SONG Chunhong³

1. Department of Pharmacy, The Affiliated Hospital of Qingdao University, Gingdao 266001, China;
2. Beijing Weixinweishi Education Technology Comsenz Inc, Beijing 102200, China;
3. Lab of Traditional Chinese Medicine Classical Theory, Ministry of Education;Shandong University of Traditional Chinese Medicine, Jinan 250355, China

Received:2020-04-30 Online:2020-12-25 Published:2020-12-30

摘要/Abstract

摘要： 目的基于L型电压依赖型钙通道探讨芍药苷改善大鼠抑郁焦虑样行为的药理作用机制。方法 48只大鼠分为正常组,L型钙通道激动剂Bayk8644组,芍药苷高、中、低剂量组（200 mg·kg^-1·d^-1、100 mg·kg^-1·d^-1、50 mg·kg^-1·d^-1）,阳性对照尼莫地平组（1 mg·kg^-1·d^-1）。正常组和Bayk8644组给予相同剂量的0.9%NaCl溶液,其余组给予相应药物。连续给药7 d后,除正常组外,其余组腹腔注射Bayk8644（0.2 mg·kg^-1·d^-1）。利用旷场实验和高架十字迷宫实验评价大鼠行为学变化,蛋白质印迹法检测海马体脑区钙调蛋白依赖的蛋白激酶Ⅱ（calmodulin-dependent protein kinase type Ⅱ,CaMKⅡ）、磷酸化的CaMKⅡ（pho-CaMKⅡ）和脑源性神经营养因子（brain-derived neurotrophic factor, BDNF）的表达水平。结果与正常组大鼠相比,Bayk8644组大鼠旷场总路程、中央区停留时间、中央区总路程及直立次数均明显下降（P<0.05或P<0.01）,大鼠进入开放臂次数百分比（OE%）和时间百分比（OT%）明显降低（P<0.05或P<0.01）,CaMKⅡ、pho-CaMKⅡ蛋白表达水平明显升高（P<0.05或P<0.01）,BDNF蛋白表达水平明显降低（P<0.05）。与Bayk8644组相比,芍药苷高、中剂量组旷场总路程延长,直立次数明显增多（P<0.05）,芍药苷高剂量组中央区总路程明显延长（P<0.05）,芍药苷高、中、低剂量组中央区停留时间明显延长（P<0.05）,芍药苷高剂量组的OE%、OT%（P<0.05或P<0.01）和芍药苷中剂量组的OT%明显升高（P<0.05）,芍药苷高剂量组大鼠CaMKⅡ和pho-CaMKⅡ蛋白表达水平明显降低（P<0.05或P<0.01）,而BDNF蛋白表达水平明显升高（P<0.05）。结论 Bayk8644能引起大鼠抑郁焦虑样表现,芍药苷能拮抗Bayk8644的作用。芍药苷可能通过抑制L型钙通道影响CaMKⅡ蛋白的活化,从而发挥其药理作用。

关键词: 芍药苷, 钙通道, Bayk8644, 抑郁, 焦虑, 钙调蛋白依赖的蛋白激酶Ⅱ, 大鼠

Abstract: Objective To explore the mechanism of paeoniflorin in improving depression and anxiety of rats through L-type calcium channel. Methods Forty-eight rats were divided into a normal group, a Bayk8644 (L-type Ca²⁺ channel agonist) group, and high dose (200 mg·kg^-1·d^-1), middle dose (100 mg·kg^-1·d^-1) and low dose (50 mg·kg^-1·d^-1) paeoniflorin groups, and a positive control nimodipine group (1 mg·kg^-1·d^-1). The normal group and the Bayk8644 group were given normal saline, and the other groups were given corresponding drugs. After 7 days of continuous administration, Bayk8644 (0.2 mg·kg^-1·d^-1) was injected intraperitoneally into all the groups except the normal group. The open field test (OFT) and elevated plus maze test (EPM) were used to test the depression and anxiety behavior of rats. The expression levels of calmodulin-dependent proteins kinase type Ⅱ (CaMK Ⅱ), brain-derived neurotrophic factor (BDNF) and phosphorylated CaMK Ⅱ (pho-CaMK Ⅱ) in each group were detected by Western blotting. Results Compared with the normal group, the total distance, the time spent in the central area, the distance in the central area, the number of vertical movement, the percentage of open arm time (OT%) and the percentage of open arm entry (OE%) of the Bayk8644 group increased significantly (P<0.05 or P<0.01), the expression levels of CaMKⅡ and pho-CaMK Ⅱ increased significantly (P<0.05 or P<0.01), and the expression level of BDNF decreased significantly (P<0.05). Compared with the Bayk8644 group, the total distance in the central area of the high dose paeoniflorin group increased significantly (P<0.05), the time spent in the central area of the middle and high dose paeoniflorin groups were extended (P<0.05), the OT% and OE% of the high dose paeoniflorin group and the OT% of the middle dose paeoniflorin group decreased significantly (P<0.05 or P<0.01), the expression levels of CaMKⅡ and pho-CaMK Ⅱ proteins in the high dose paeoniflorin groups were significantly reduced (P<0.05 or P<0.01), and the expression level of BDNF protein was significantly increased (P<0.05). Conclusion Bayk8644 can induce depression and anxiety behavior of rats. Paeoniflorin can antagonize the negative effect of Bayk8644 and exert its pharmacological effect by inhibiting the L-type calcium channel and influenceing the activation of CaMKⅡ protein.

Key words: Paeoniflorin, Calcium channel, Bayk8644, Depression, Anxiety, Calmodulin-dependent protein kinase typeⅡ, Rats

中图分类号:

Q95-33

李萍, 李艺杰, 薛玲, 宋春红. 芍药苷对Bayk8644诱导大鼠抑郁焦虑样行为的改善作用及机制研究[J]. 实验动物与比较医学, 2020, 40(6): 489-495.

LI Ping, LI Yijie, XUE Ling, SONG Chunhong. Effect and Mechanism of Paeoniflorin on Depression and Anxiety Behavior Induced by Bayk8644 in Rats[J]. Laboratory Animal and Comparative Medicine, 2020, 40(6): 489-495.

图/表 4

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芍药苷对Bayk8644诱导大鼠抑郁焦虑样行为的改善作用及机制研究

Effect and Mechanism of Paeoniflorin on Depression and Anxiety Behavior Induced by Bayk8644 in Rats

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