Abstract:

Objective: To study the antidepressant effect of Baihe Zhimu decoction (BZD) and its influence in the key factors(CaM,CaMKⅡ,CREB) of CaM signaling pathway in hippocampus of the rats with depression,and to explore the antidepressant effect of BZD. Methods: Fifty rats were divided into control group,model group,fluoxetine group,low and high doses of BDZ groups (n=10).Expect for control group,all the rats in other groups were made depression models by means of chronic unpredictable mild stress along with isolated raising,for 21 d. Then the rats were fed with NS,fluoxetine(1.8 mg·kg^-1),and BZD(1.5 and 3.0 g·kg^-1),respectively;for 28 d.The learning and memory ability,autonomous activities and the fixed time in 5 min of the rats were tested by Morris water amaze,Open-field Test and Forced Swimming Test respectively. The damage and repair status of hippocampal neurons were observed by Nissl staining method;the expression levels of CaM,CaMKⅡ protein,CREB mRNA in hippocampus of the rats were detected by Western blotting and RT-PCR method. Results: Compared with model group,the total time of rats in the platform quadrant of Morris water maze in BZD groups and fluoxetine group,the total distance and the number of crossing platform were increased (P < 0.05 or P < 0.01),and the time of first crossing platform were shortened(P < 0.01);the total scores in open field test were increased (P < 0.01),the fixed time with 5 min in the forced swimming test was shortened (P < 0.05 or P < 0.01).Compared with fluoxetine group,the fixed time within 5 min of the rats in swimming test was shortened(P < 0.05).The result of Nissl staining showed that the hippocampal neuron injury in BZD groups and fluoxetine group was improved compared with model group.The molecular test results showed that the CaM and CaMKⅡ protein expression levels in hippocampus of the rats in BZD groups and fluoxetine group were increased compared with model group(P < 0.05 or P < 0.01).Compared with model group,the CREB mRNA expression levels in fluoxetime group and BZD groups were increased(P < 0.05 or P < 0.01). Conclusion: BZD has antidepressant effect and can improve the hippocampal neuron injury of the rats with depression and its mechanism is related to increasing the expression levels of CaM,CaMKⅡ and CREB in hippocampus CAM signaling pathway of the rats.

Key words: depression, Baihe Zhimu decoction, calmodulin, calmodulin kinase Ⅱ, response element binding protein