Serum Levels Of Brain-Derived Neurotrophic Factor And Vascular Endothelial Growth Factor In Rat Model Of Depression Before And After Antidepressant Treatment

[Objectives] The cause of depression is still unknown. Numerous studies have demonstrated that depression may be highly associated with neurogenesis and neurotrophy. Brain-derived neurotrophic factor(BDNF) and vascular endothelial growth factor(VEGF) involved in neurogenesis process. Through the establishment of a depression rat model to study the changes in relationships with BDNF and VEGF, and antidepressant treatment of depression, to explore the neurotrophic hypothesis of depression, provide a reference to the possible biological markers and effective interventions.[Methods] Sprague-Dawley male rats was used in establishing chronic unpredictable mild stress (CUMS) model, the classic model of depression. High fat diet superimposed with CUMS to established vascular depression model (VD), and the normal rats (NC) as control. Two groups of depression model rats were randomly divided into 4 groups and given fluoxetine, Salvia Miltrorrhiza, co-medication (fluoxetine+Salvia Miltrorrhiza) and saline intervention treatment for 4 weeks. Before and after drug intervention were the rats serum collected, BDNF and VEGF levels were determined by enzyme-linked immunosorbent assay. Observe open-field test behavioral parameters, including the number of first minute activity and the number of grooming, analyze their relevance with BDNF and VEGF. The groups were compared using one-way ANOVA; relevance was analyzed by Pearson correlation.[Results] ① Serum BDNF levels in CUMS rat model of depression (3261.8+ 517.7 pg/ml) and in VD model rats (3627.0±339.5 pg/ml) are lower than the control group (3757.0±486.2 pg/ml), although the difference was not statistically significant (F=0.319, p=0.733).VEGF concentration differences was not significant (F=0.062, p=0.940); ② BDNF levels in the CUMS model rats after interventions there was no significant difference between 4 ways of intervention(F=1.14, p=0.361), but BDNF in Salvia treatment group (3412.6±284.7 pg/ml) tend higher than in fluoxetine treatment group (2567.5±422.7pg/ml) and in co-medication group (2550.2±582.6 pg/ml);no significant differences in the levels of VEGF(F=0.114, p=0.950;③ In VD model of rats after intervention, the difference of BDNF and VEGF levels s were not significant among the 4 groups (BDNF:F=1.539, p=0.234; VEGF:F=0.193, p=0.900), but Salvia treatment group BDNF (1901.1±69.7 pg/ml) tend higher than fluoxetine treatment group (1485.2±72.9 pg/ml);④Correlation between BDNF and VEGF levels was not statistically significant (r=0.048, p= 0.711);⑤ Correlation between serum BDNF levels of CUMS model and open-field experiment the number of first minute activity was positive related(r=0.949, p=0.014);and the number of grooming was negatively correlated with BDNF of CUMS model(r=-0.933, p=0.021).[Conclusions]① Depression model has lower BDNF levels, especially in CUMS model, suggesting there might be neurotrophic dysfunction in depression; ② Salvia treatment may improve neurotrophic function through its cerebral vascular protecting function, relieve the symptoms of depression, especially for depression with vascular factors, the exact mechanism needs further study.