主 办:北 京 中 医 药 大 学
ISSN 1006-2157 CN 11-3574/R

北京中医药大学学报 ›› 2020, Vol. 43 ›› Issue (3): 212-217.doi: 10.3969/j.issn.1006-2157.2020.03.006

• 中药药理 • 上一篇    下一篇

松郁安神方对失眠大鼠海马cAMP/PKA信号通路的影响*

李璟怡1, 黄俊山2,3,4#, 陈沁1, 王秀峰2,3,4, 张瑜2,3,4, 张一帆2,3,4   

  1. 1 福建中医药大学 福建 350122;
    2 福建省中医药研究院;
    3 黄俊山福建省名老中医药专家传承工作室;
    4 福建省中医睡眠医学重点实验室
  • 收稿日期:2019-06-05 发布日期:2020-04-13
  • 通讯作者: 黄俊山,男,博士,教授,主任医师,博士生导师,研究方向:中西医结合治疗睡眠障碍相关疾病,E-mail:hjsh0825@163.com
  • 作者简介:李璟怡,女,硕士,讲师
  • 基金资助:
    *国家科技部重点研发计划项目(No.2018YFC17056),国家自然科学基金项目(No.81774285),福建省自然科学基金项目(No.2016J01393),福建省省属公益类专项(2017R1035-5),福建中医药大学校管课题(No.X2014015)

Effects of Songyu Anshen Fang on cAMP/PKA signaling pathways in hippocampus of insomnia rats*

Li Jingyi1, Huang Junshan2,3,4#, Chen Qin1, Wang Xiufeng2,3,4, Zhang Yu2,3,4, Zhang Yifan2,3,4   

  1. 1 Fujian University of Traditional Chinese Medicine, Fujian 350122, China;
    2 Fujian Academy of Traditional Chinese Medicine, Fujian 350003, China;
    3 Office of Inheritance of Fujian Famous Traditional Chinese Medicine Expert Huang Junshan, Fujian 350003, China;
    4 Fujian Key Laboratory of Sleep Medicine of Traditional Chinese Medicine, Fujian 350003, China
  • Received:2019-06-05 Published:2020-04-13
  • Contact: Prof. Huang Junshan, Ph.D., Chief Physician, Doctoral Supervisor. Fujian Academy of Traditional Chinese Medicine, Office of Inheritance of Fujian Famous Traditional Chinese Medicine Expert Huang Junshan, Fujian Key Laboratory of Sleep Medicine of Traditional Chinese Medicine. No.282 Wusi Road, Gulou District, Fuzhou 350003. E-mail:hjsh0825@163.com

摘要: 目的 探讨松郁安神方对失眠大鼠海马5-羟色胺1A受体(5-HT1AR)介导的环磷酸腺苷(cAMP)信号通路的影响,明确其作用靶点。方法 50只SD大鼠,随机分为对照组、模型组、松郁安神方低剂量组、松郁安神方高剂量组和丁螺环酮组,每组10只。除对照组外,其余4组采用慢性夹尾刺激和腹腔注射对氯苯丙氨酸(PCPA)建立肝郁失眠大鼠模型。造模成功后,除正常组和模型组外,松郁安神方低剂量组(8.5 g/kg)、松郁安神方高剂量组(17 g/kg)和丁螺环酮组(2.0 mg/kg)按相应剂量灌胃,1次/d,连续14 d。模型组和对照组以等量生理盐水灌胃,频次、时间同前。给药期间,观察大鼠一般状态;给药结束后,观察大鼠体质量、敞箱实验变化,检测各组5-HT1AR及cAMP、蛋白激酶A(PKA)基因和蛋白的表达。结果 与对照组相比,模型组大鼠敞箱实验中央格停留时间、修饰次数、大便颗粒数上升(P<0.05),海马5-HT1AR、cAMP、PKA mRNA及蛋白表达均明显降低(P<0.05)。不同剂量松郁安神方干预后,和模型组相比,松郁安神方高剂量组敞箱实验中央格停留时间、修饰次数、粪便颗粒数均减少,5-HT1AR、cAMP、PKA mRNA及蛋白表达均升高(P<0.05);松郁安神方低剂量组敞箱实验中央格停留时间、修饰次数、粪便颗粒数减少,5-HT1AR、PKA和cAMP mRNA及蛋白表达上调(P<0.05);高剂量组各项指标与丁螺环酮组比较差异无统计学意义(P>0.05)。结论 松郁安神方改善肝郁失眠大鼠睡眠的机制可能是通过海马5-HT1AR介导的cAMP信号通路发挥作用。

关键词: 松郁安神方, 失眠, 5-羟色胺1A受体, cAMP/PKA信号通路, 大鼠

Abstract: Objective To explore the effects of Songyu Anshen Fang (Radix et Rhizoma Nardostachyos and Radix Curcumae Spirit-calming Formula, SYASF) on 5-hydroxytryptamine 1A receptor (5-HT1AR) and cAMP signaling pathways in hippocampus of insomnia rats and to identify possible targets of such effects. Methods Fifty SD rats were randomly divided into control group, model group, low-dose SYASF group, high-dose SYASF group and buspirone group, with 10 rats in each group. Except the control group, rat models of liver constraint and insomnia were established in the other four groups with long-term tail-clip stimulation and intraperitoneal injection of chlorphenylalanine (PCPA). After the establishment of models, corresponding medicinals were administered to the low-dose SYASF group (8.5 g/kg), high-dose SYASF group (17 g/kg) and buspirone group (2.0 mg/kg) by gavage once a day for 14 consecutive days. Normal saline was given to the model group and the control group with the same frequency and duration. The general state of rats was observed during administration. By the end of administration, changes in body mass and results of open-field tests of the rats were observed and expressions of genes and proteins of 5-HT1AR, cAMP and PKA in all groups were detected. Results Compared with the control group, the time spent in the central area, number of grooming and number of fecal particles of the model group in the open field test were increased (P<0.05), and the expressions of 5-HT1AR, cAMP, PKA mRNA and protein in hippocampus of the model group were all decreased (P<0.05). Compared with the model group, the time spent in the central area, number of grooming and number of fecal particles of the high-dose SYASF group were reduced, while the mRNA and protein expressions of 5-HT1AR, cAMP, PKA increased (P<0.05). In the low-dose SYASF group, the time spent in the central area, number of grooming and number of fecal particles were decreased, while the mRNA and protein expressions of 5-HT1AR, PKA and cAMP were elevated (P<0.05), compared with the model group. There was no statistically significant difference between the high-dose SYASF group and the buspirone group (P>0.05). Conclusion SYASF can improve sleep of rats with liver constraint and insomnia, and its mechanism may be regulation through the cAMP/PKA signaling pathways mediated by 5-HT1AR in the hippocampus.

Key words: Songyu Anshen Fang, insomnia, 5-HT1A receptor, cAMP/PKA signaling pathway, rats

中图分类号: 

  • R285.5