Behavioral and Neurochemical Changes in Rats with Recurrent Depression induced by chronic unpredictable stress.

OBJECTIVES: The mechanism of recurrent depression remains unclear. This study aimed to evaluate the behavioural and neurochemical patterns of rats with recurrent depression. MATERIALS AND METHODS: An animal model of recurrent depression was established using chronic unpredictable stress and imipramine hydrochloride. The behaviour of the rats was tested during the first onset and recurrence periods of depression. The levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), and cyclic adenosine monophosphate (cAMP) in serum were detected by ELISA. The protein expressions of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) in the hippocampal dentate gyrus (DG) area of rats were detected by western blotting. RESULTS: The weight and sugar preference of the rats with recurrent depression were significantly decreased, and the immobility time of tail suspension was significantly increased during the first onset and recurrence periods. The modelling time of rats was shortened by one week in the recurrence period compared with that in the first onset. The model rats with recurrent depression had significantly increased ACTH and CORT and significantly decreased cAMP, CREB, and BDNF levels. CONCLUSION: Rats with recurrent depression are highly susceptible to stress and exhibit depression-like behaviours such as weight loss, increased immobility time in tail suspension test, and reduced sucrose preference index. Moreover, the modelling time was shortened by one week, indicating an obvious susceptibility to recurrent depression. The significantly up-regulated neuroendocrine in the HPA and the significantly inhibited BDNF and protein expression factors in related signalling pathways may be involved in the increased susceptibility to recurrent depression.

Anti-tumor and apoptotic effects in vitro and in vivo of a traditional Chinese medicine prescription.

BACKGROUND: Zhongfei Mixture (ZM), a traditional Chinese medicine, exploited from the clinical experience, has mainly been used for the treatment of advanced lung cancer since it was produced in 1983. However, little research has been conducted on its anti-tumor mechanism. In this study, we aimed to investigate the anti-tumor and apoptotic effects of ZM in vitro and in vivo. METHODS: The growth inhibition effect of ZM on A549 cells was evaluated by MTT assay. Morphological observation and clone forming tests were performed to determine the effect of ZM on cell viability. Cell cycle distribution and apoptosis were analyzed by flow cytometry. In addition, the in vivo anti-proliferation activity of ZM was evaluated using mice bearing Lewis lung carcinoma. Further, the apoptosis of cells in tumor tissue was determined by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, and the expression of Ki-67 protein in tumor tissues was analyzed by En-Vision immuno-histochemistry staining. RESULTS: ZM exerted an obvious inhibitory effect on proliferation of A549 cells. It arrested A549 cells in G(2)-M phase and induced apoptosis. Compared with 3.02% and 5.32% in control group, the percentages of cells arrested in G(2)-M phase were 19.20% and 19.58% in 7.94 mg/ml ZM treated A549 cells at 24 hours and 48 hours. Moreover, the apoptosis rate increased from 0.18% to 18.01% after ZM treatment for 48 hours. ZM also significantly inhibited tumor growth in the tumor-implanted mice. Compared with saline control group, the effects of ZM showed significant tumor growth inhibition (P < 0.05). Furthermore, ZM could down-regulate the expression of Ki-67 in tumor tissue in mice bearing Lewis lung carcinoma. CONCLUSIONS: Our results indicated that ZM has notable anti-tumor effect and the effects of ZM in moderate dose groups were superlative both in vitro and in vivo. The possible mechanism of ZM might be associated with arresting cell cycle in G(2)-M phase as well as down-regulating Ki-67 expression in tumor tissues.