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

JOURNAL OF BEIJING UNIVERSITY OF TRADITIONAL CHINESE MEDICINE ›› 2019, Vol. 42 ›› Issue (5): 396-403.doi: 10.3969/j.issn.1006-2157.2019.05.007

Previous Articles     Next Articles

Influence of Zuogui Jiangtang Jieyu Fang on expressions of hippocampal NVU connexins in rats with diabetes mellitus complicated by depression*

Huang Huizhen1, Liu Zhuo1, Han Yuanshan2, Zhao Hongqing1,3, Jin Shi1, Luo Weixu1, Meng Pan1,3, Wang Yuhong1,3#   

  1. 1 Training Base of Province-Ministry Joint State Key Laboratory of Chinese Medicinal Powder and Innovative Medicinals, Hunan University of Chinese Medicine, Hunan 410208, China;
    2 First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410007, China;
    3 Science and Technology Innovation Center, Hunan University of Traditional Chinese Medicine, Hunan 410208, China
  • Received:2018-11-06 Online:2019-05-30 Published:2019-06-05
  • Contact: Wang Yuhong, Ph. D., Researcher, Doctoral Supervisor. Training Base of Province-Ministry Joint State Key Laboratory of Chinese Medicinal Powder and Innovative Medicinals, Science and Technology Innovation Center, Hunan University of Chinese Medicine, No. 300, Xueshi Road, Hanpu Science and Education Park, Yuelu District, Changsha 410208. E-mail: wyh107@126.com

Abstract: Objective To discuss the influence of Zuogui Jiangtang Jieyu Fang (ZHJYF, Left-Restoring Sugar-lowering Depression-relieving Formula), based on neurovascular unit (NVU), on the expressions of tight junction proteins and connexins in rats with diabetes mellitus (DM) complicated by depression. Methods Adult SD rats (n=70) were orally given high-fat emulsion, injection of streptozocin (STZ) in caudal vein and chronic unpredicted stress to establish the model of DM complicated by depression. The rats were randomly divided into 5 groups: model group, metformin+fluoxetine group, high-dose, mid-dose and low-dose ZHJYF groups. Other 12 unmodeling rats were chosen into blank control group. All group were orally given corresponding medicinals at the same time of stress for 28 d. The level of autonomic activity and learning-memory ability were reviewed by using open-field test and Morris water maze (MWM), and morphologic structure of hippocampal NVU was observed by using transmission electron microscope (TEM). The expressions of tight junction proteins (Claudin-1 and Occluding), connexins [aonnexin43 (CX43) and aquaporin4 (AQP4)] were detected by using immunohistochemistry technique and RT-qPCR. Results Compared with blank control group, the times of autonomic activity and space exploration time decreased significantly and escape latency was prolonged significantly in model group (P<0.01). The results of TEM and pathology showed that swollen hippocampal endothelial cells, confused perivascular tight and gap junctions and loosely arranged cells, and the protein and mRNA expressions of Claudin-1, Occludin, CX43 and AQP4 decreased significantly in model group (P<0.01). Compared with mode group, the times of autonomic activity and space exploration time increased significantly and escape latency was shortened significantly (P<0.05 or P<0.01), swelling of hippocampal endothelial cells was relieved, perivascular tight and gap junctions was recovered, and cell arrangement was tidiness, and the protein and mRNA expressions of Claudin-1, Occludin, CX43 and AQP4 increased significantly in high-dose ZHJYF group (P<0.05 or P<0.01). Conclusion ZHJYF can significantly relieve depressive behavior in rats, and the mechanism may be related to enhance of expressions of tight junction proteins and connexins and maintain the structure and function of hippocampal NVU.

Key words: Zuogui Jiangtang Jieyu Fang (Left-Restoring Sugar-lowering Depression-relieving Formula), diabetes mellitus complicated by depression, hippocampal neurovascular unit, tight junction proteins, connexins, rats

CLC Number: 

  • R285.5