舒郁胶囊及其主要组份对经前期综合征肝气郁证大鼠海马中Cav1.2介导的CaM/CaMKⅡ信号通路的影响

doi:10.3969/j.issn.1674-5817.2019.05.007

实验动物与比较医学 ›› 2019, Vol. 39 ›› Issue (5): 377-382.DOI: 10.3969/j.issn.1674-5817.2019.05.007

舒郁胶囊及其主要组份对经前期综合征肝气郁证大鼠海马中Cav1.2介导的CaM/CaMKⅡ信号通路的影响

徐凯勇¹, 王杰琼¹, 李芳², 耿燕楠³, 夏小雯¹, 宋春红¹

1.山东中医药大学, 教育部中医药经典理论研究重点实验室,山东省中医药基础研究重点实验室, 济南 250355;
2.北京市丰台区妇幼保健院药剂科, 北京 100067

收稿日期:2019-02-18 出版日期:2019-10-25 发布日期:2021-01-05
作者简介:徐凯勇(1980-), 男, 硕士, 中药药理研究。E-mail: xkychina@163.com
基金资助:
国家自然科学基金项目(81473359), 山东省中医药科技发展计划项目(2017-087), 山东中医药大学大型仪器设备专项(2018yq02)

The Effects of Shu Yu Capsule and Its Main Composition on Cav1.2 Mediated CaM/ CaMKⅡSignaling Pathway in Hippocampus of Rat with PMS Liver-qi Stagnation

XU Kai-yong¹, WANG Jie-qiong¹, LI Fang², GENG Yan-nan³, XIA Xiao-wen¹, SONG Chun-hong¹

1. Lab of Traditional Chinese Medicine Classical Theory, Ministry of Education;Key Laboratory of Basic Traditional Chinese Medicine Research in Shandong Province;Shandong University of Traditional Chinese Medicine, Jinan 250355, China;
2. Department of Pharmacy, Fengtai District Maternal and Child Health Care Hospital, Beijing 100067, China;
3. The Affiliated Hospital of Shandong University of TCM Jinan 250355, China

Received:2019-02-18 Published:2019-10-25 Online:2021-01-05

摘要/Abstract

摘要： 目的探讨L型钙通道(Cav1.2)下游信号通路中钙调蛋白/钙调蛋白依赖的蛋白激酶Ⅱ(CaM/ CaMKⅡ)与经前期综合征(PMS)肝气郁证的关系以及舒郁胶囊的干预机制。方法用舒郁胶囊、柴胡提取物、白芍提取物和阳性对照氟西汀+尼莫地平对慢性束缚应激法制备的PMS肝气郁证大鼠进行干预,免疫印迹技术检测各组海马中CaM,CaMKⅡ的磷酸化水平及脑源性营养因子(BDNF)蛋白表达。结果慢性束缚应激可以成功复制PMS肝气郁证大鼠模型。蛋白表达结果显示,模型组大鼠海马中CaM蛋白的表达量升高(P<0.05),CaMKⅡ磷酸化水平显著升高, BDNF蛋白的表达量显著下降(P<0.01)。与模型组相比,氟西汀+尼莫地平组大鼠海马CaM蛋白表达量显著降低(P<0.05),各给药组海马中CaMKⅡ磷酸化水平显著下降(P<0.01),BDNF的蛋白表达量均显著升高(P<0.01, P<0.05)。结论海马脑区Cav1.2下游信号通路中CaM/ CaMKⅡ的激活与PMS肝气郁证的发生有关,舒郁胶囊及其有效组分可能是通过抑制CaMKⅡ信号通路的激活发挥其治疗作用。

关键词: 经前期综合征(PMS), 舒郁胶囊, 白芍提取物, 柴胡提取物, L型钙通道 (Cav1.2)

Abstract: Objective To study the relationship of L-type calcium channel (Cav1.2) mediated calmodulin/calmodulin-dependent protein kinase II (CaM/CaMKII) signaling pathway with premenstrual syndrome (PMS) with liver-qi stagnation, and elucidate the Shuyu capsule intervention mechanism. Methods The PMS model rats with liver-qi stagnation were induced by bondage stimulation, and the model rat were treated with Shuyu capsule, the extract from Radix Bupleuri and Radix Paeoniae, and fluoxetine+nimodipine as positive control. The experiment were divided into six groups: normal group, model group, Shuyu group, Radix Bupleuri, Radix Paeoniae group and fluoxetine+nimodipine group. The expression level of CaM, brain-derived neurotrophic factor (BDNF) and phosphorylation level of CaMKII were detected by Western blotting. Results Compared with the normal group, the protein expression level of p-CaMK II increased and BDNF decreased significantly in hippocampus of model rats. After treating with our medication the protein expression of CaM and CaMK II phosphorylation level decreased obviously, the expression level of BDNF increased markedly (P<0.05; P<0.01). Conclusion We hypothesized that the CaM/CaMKⅡcalcium signal pathway mediated by Cav1.2 may play important role in the pathogenesis of PMS Liver-qi stagnation and maybe the molecular targets of Shuyu capsule to treatment PMS with Liver-qi stagnation.

Key words: Premenstrual syndrome, Shuyu Capsule, Radix Bupleuri extract, Radix Paeoniae extract, L-type calcium channel (Cav1.2)

中图分类号:

Q95-33

徐凯勇,王杰琼,李芳,等. 舒郁胶囊及其主要组份对经前期综合征肝气郁证大鼠海马中Cav1.2介导的CaM/CaMKⅡ信号通路的影响[J]. 实验动物与比较医学, 2019, 39(5): 377-382. DOI: 10.3969/j.issn.1674-5817.2019.05.007.

XU Kai-yong,WANG Jie-qiong,LI Fang,et al. The Effects of Shu Yu Capsule and Its Main Composition on Cav1.2 Mediated CaM/ CaMKⅡSignaling Pathway in Hippocampus of Rat with PMS Liver-qi Stagnation[J]. Laboratory Animal and Comparative Medicine, 2019, 39(5): 377-382. DOI: 10.3969/j.issn.1674-5817.2019.05.007.

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舒郁胶囊及其主要组份对经前期综合征肝气郁证大鼠海马中Cav1.2介导的CaM/CaMKⅡ信号通路的影响

The Effects of Shu Yu Capsule and Its Main Composition on Cav1.2 Mediated CaM/ CaMKⅡSignaling Pathway in Hippocampus of Rat with PMS Liver-qi Stagnation

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