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

JOURNAL OF BEIJING UNIVERSITY OF TRADITIONAL CHINESE MEDICINE ›› 2021, Vol. 44 ›› Issue (5): 444-453.doi: 10.3969/j.issn.1006-2157.2021.05.009

• Chinese Medicinal Pharmacology • Previous Articles     Next Articles

Effects and efficacy of Compound Chaijin Jieyu Formula on the expression of CaMKⅡ and CREB in hypothalamus and hippocampus of rats with depression and insomnia*

Wang Yeqing1, Wang Yuhong1#, Huang Huizhen1, Zou Manshu1, Liu Can1, Li Chunyan1, Zhao Hongqing1, Liu Jian2   

  1. 1 Institute of Scientific Innovation and Applied Research,Hunan University of Chinese Medicine, Hunan 410208, China;
    2 The First Hospital of Hunan University of Chinese Medicine, Hunan 410007, China
  • Received:2020-09-05 Online:2021-05-30 Published:2021-06-01
  • Contact: Prof.Wang Yuhong, M.D., Doctoral Supervisor. Institute of Scientific Innovation and Applied Research, Hunan University of Chinese Medicine. No. 300 Xueshi Road, Hanpu Science and Education Park, Yuelu District, Changsha 410208. E-mail: wyh107@126.com
  • Supported by:
    National Science and Technology Major Project for Research and Development of Major New Drugs (No.2017ZX09309026), Natural Science Foundation of Hunan Province (No.2019JJ50428), General Project of Hunan Provincial Education Department (No.18C0371, No.18C0392), Key Project of Hunan Provincial Science & Technology Department (No.2018DK2014), Innovation Project for Graduate Students in Hunan Province (No.CX20200763)

Abstract: Objective To observe the effect of Compound Chaijin Jieyu(Bupleurum & Turmeric Root Tuber Depression-Relieving) Formula (CCJJYF) on the expression of Calmodulin-Dependent Protein Kinase Ⅱ (CaMKⅡ) and cAMP-response-element-binding protein (CREB) in hypothalamus and hippocampus of rats with depression and insomnia, and to explore the mechanism of CCJJYF in relieving depression and insomnia. Methods 72 SD rats were randomly divided into normal group, model group,venlafaxine (13.5 μg/g)+diazepam (0.9 μg/g) group, high-dose (10.8 g/kg) CCJJYF group, mid-dose (5.4 g/kg) CCJJYF group and low-dose (2.7 g/kg) CCJJYF group (n=12). Chronic unpredictable mild stress (CUMS) combined with sleep deprivation was used to establish rat models of depression and insomnia. After 35 days of modeling and drug intervention, forced swim test (FST) and pentobarbital sodium test were used to detect depression and insomnia-like behaviors in rats. HE staining was used to detect the pathological changes in hypothalamus and hippocampus. The levels of CRH, ACTH and CORT in serum and hypothalamus were detected by ELISA. In addition, the levels of NE, 5-HT and DA in hypothalamus and hippocampus were detected by HPLC-ECD. Western blot and RT-qPCR were used to detect the protein level of CaMKⅡ and CREB and their gene expression in the hypothalamus and hippocampus. Results Compared with the normal group, the immobility time of rats in the model group was increased in the FST (P<0.01); besides, their sleep latency was prolonged, and their sleep duration was shortened (P<0.01). Compared with the model group, the immobility time in the mid-dose CCJJYF group was reduced in FST (P<0.01), their sleep latency was shortened, and their sleep duration increased (P<0.05). After the intervention of venlafaxine+diazepam and CCJJYF, the gap between hypothalamic and hippocampal neurons was reduced, the incidence of arrangement disorder and cell vacuoles was reduced.The levels of CRH, ACTH and CORT in serum and hypothalamus in the high-dose and mid-dose CCJJYF groups were reduced (P<0.01). The levels of NE, 5-HT and DA in the hypothalamus and hippocampus in the venlafaxine+diazepam group and the high-dose and mid-dose CCJJYF groups were increased (P<0.01). CaMKⅡ and CREB proteins and their gene expression in the hypothalamus and hippocampus in the venlafaxine+diazepam group and the mid-dose CCJJYF group increased (P<0.05 or P<0.01). Conclusion CCJJYF seems to alleviate depression-like behaviors in rats with depression and insomnia and improve their sleep quality. The mechanism may be related to reducing excessive secretion of HPA axis, stabilizing the expression of monoamine neurotransmitters and up-regulating CaMKⅡ and CREB protein and their gene expression.

Key words: Compound Chaijin Jieyu Formula(CCJJYF), depression and insomnia, hippocampus, hypothalamus, CaMKⅡ, CREB, rats

CLC Number: 

  • R285.5