ABSTRACT
This study is to investigate the effect of antidepressant medicine prescription Dingzhi Xiaowan (DZ) on miR-16 expression levels in vitro and in vivo, and to explore the mechanism of DZ elevated levels of 5-HT from the perspective of post transcriptional regulation. Firstly, a chronic unpredictable mild moderate stimulation (CUMS) combined with solitary rising depression rat model was established, the behavior changes were detected after different doses of DZ (600, 300, 150 mg·kg⁻¹) given for 3 weeks, high performance liquid chromatography (HPLC) was used to detect 5-HT level in hippocampal, PCR method was used to observe the effect of DZ on the expression of SERT mRNA and miR-16 in hippocampus of CUMS rat. The effects of DZ (10, 100, 200, 500 mg·L⁻¹) on the expression of miR-16 and SERT mRNA in the cell model induced by miR-16 silencing and corticosterone or glutamate injury were observed in primary cultured hippocampal neurons of rats in vitro. It was found that 300 mg·kg⁻¹ and 600 mg·kg⁻¹ DZ could significantly improve the behavioral score of CUMS rats, increase the level of 5-HT in hippocampus, and increase the expression of miR-16 and decrease the expression of SERT in the hippocampus of rats. At the same time, in primary cultured hippocampal neurons, 100, 200, 500 mg·L⁻¹ of DZ could significantly increase the expression level of miR-16 in miR-16 silencing and corticosterone or glutamate injury cell model, and decrease the expression level of SERT significantly. So DZ could inhibit the reuptake of 5-HT by inhibiting the expression of SERT by up regulating the expression level of miR-16, and finally increase the level of 5-HT in the brain and exert antidepressant effect.