Effects of Kaixinjieyu, a Chinese herbal medicine preparation, on neurovascular unit dysfunction in rats with vascular depression.
BACKGROUND
Kaixinjieyu (KJ), derived from Kaixin and Sini powder, is an effective Chinese herbal medicine preparation used in the treatment of vascular depression (VD). We hypothesize that broad antidepressant effect of KJ results from the improved neurovascular unit (NVU) function via neurogenesis, permeability of blood-brain barrier (BBB) and balance of the fibrinolytic system.


METHODS
A VD model of rat was established by chronic unpredictable mild stress and separation after ligation of the bilateral common carotid arteries. The rats were treated with KJ and fluoxetine hydrochloride (FLU) for 21 days, respectively. The behavior and cerebral perfusion were investigated and then NVU functions including neurogenesis, permeability of BBB and balance of the fibrinolytic system were studied using a number of biomarkers and TUNEL assay.


RESULTS
KJ significantly increased sucrose preference, moving distance, number of rearing and cortical blood flow. NVU functions measured by brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) and tissue plasminogen activator (t-PA) proteins and mRNA, zona occludens protein-1 (ZO-1), occludin and claudin-5 proteins increased significantly, whereas, plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-2 (MMP-2) proteins, mRNA and apoptotic rates of neurons decreased significantly with treatment of KJ. FLU has a function similar to KJ in behavior, regulation of BDNF, TrkB, MMP-2, occludin and apoptotic rates of cells.


CONCLUSIONS
KJ has function of reducing depression-like behavior and improving cerebral hypoperfusion, which might be mediated by the up-regulation of neurogenesis and tight junction of BBB, and balance of the fibrinolytic system. The results imply that KJ is better than FLU in improving cerebral hypoperfusion and the fibrinolytic system.
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China. panjuhua@126.com.
Juhua
J
Pan
Huangpi District Hospital of Traditional Chinese Medicine, Wuhan, Hubei, 430300, China. leixiaoming66@126.com.
Xiaoming
X
Lei
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China. footprint666@163.com.
Jialong
J
Wang
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China. gamhsj@126.com.
Shijing
S
Huang
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China. gamwyy@126.com.
Yanyun
Y
Wang
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China. zhangying1179@163.com.
Ying
Y
Zhang
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China. gamwendy@163.com.
Wen
W
Chen
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China. gam_lee@126.com.
Duojiao
D
Li
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China. zhengjun_321@126.com.
Jun
J
Zheng
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China. cui-yaoshi@163.com.
Hanming
H
Cui
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China. gam-yaoyan@163.com.
Qihua
Q
Liu
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002318:Cardiovascular Diseases; D003863:Depression; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D055495:Neurogenesis / Q000187:drug effects*; D000069336:Neurovascular Coupling / Q000187:drug effects; D051381:Rats
D004365:Drugs, Chinese Herbal; C000603459:kaixin jieyu