ABSTRACT
Objective:To investigate the effect of ginkgo biloba extract (GBE) on oxidative stress in medial prefrontal cortex and excitatory/inhibitory balance of pyramidal neurons in chronic unpredictable mild stress (CUMS)-induced depressive model mice.Methods:Totally 48 SPF grade 7-week-old male C57BL/6J mice were divided into 4 groups according to random number table method: control+ saline group (CTRL+ Veh), control+ GBE group (CTRL+ GBE), model+ saline group (CUMS+ Veh), model+ GBE group (CUMS+ GBE), with 12 mice in each group.Mice in CUMS+ Veh group and CUMS+ GBE group were established by CUMS method, and mice in CTRL+ GBE group and CUMS+ GBE group were intraperitoneally injected with GBE (70 mg/kg) once a day, and mice in CTRL+ Veh group and CUMS+ Veh group were injected intraperitoneally with 0.9% sodium chloride solution.Then, the sucrose preference test, forced swimming test (FST) and tail suspension test (TST) were performed to evaluate the depressive-like behavior of mice, and open field test (OFT) was performed to evaluate the autonomous locomotion and exploration ability and anxiety-like behavior.The content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in mPFC were determined by ELISA.Spontaneous excitatory postsynaptic currents (sEPSC) and spontaneous inhibitory postsynaptic currents (sIPSC) were detected by whole-cell recording.SPSS 23.0 was used for data analysis and two-factor analysis of variance(whether to get GBE, whether to mold, show as GBE×CUMS) was used for statistical analysis.Results:(1) Behavioral results: the the time spent in center and total distance of OFT and sugar preference rate of the four groups of mice were compared, and the interaction of GBE×CUMS was significant( F=24.90, 4.82, 3.91, all P<0.05). The results of simple effect analysis showed that the time spent in center ((47.15±3.58) s), the total distance((19.33±0.86) m) and the sugar preference rate((59.11±8.79)%) of the mice in CUMS+ Veh group were lower than those in the CTRL+ Veh group((61.55±2.49) s, (23.24±1.21) m, (84.02±7.45) %) (all P<0.01), and the above indexes in CUMS+ GBE group ((56.51±3.53) s, (20.75±1.31) m, (70.80±11.79)%) were higher than those in CUMS+ Veh group (all P<0.05). In the immobility time of FST and TST of mice in the 4 groups, the interaction of GBE×CUMS were significant( F=85.53, 83.39, both P<0.01). The immobility time of FST and TST in CUMS+ Veh group were higher than those in CTRL+ Veh group (both P<0.01 ), and the above indexes in CUMS+ GBE group were lower than CUMS+ Veh group(both P<0.05). (2)The results of ELISA showed that the interaction of GBE×CUMS of SOD level of mice in the 4 groups was not significant ( F=3.52, P=0.07), but the main effects of GBE factor and CUMS factor were both significant ( F=4.69, 46.93, both P<0.05). The interaction of GBE×CUMS of MDA level was significant( F=16.61, P<0.01). The level of SOD in the CUMS+ Veh group was lower than that in the CTRL+ Veh group ( P<0.01), and the level of SOD in the CUMS+ GBE group was higher than that in the CUMS+ Veh group ( P<0.05). The level of MDA in the CUMS+ Veh group was higher than that of the CTRL+ Veh group ( P<0.01), and the level of MDA in CUMS+ GBE group was lower than that of the CUMS+ Veh group ( P<0.01). (3) The results of whole-cell recording showed that the interaction of GBE×CUMS of frequency and quantification of sEPSC in the four groups were significant ( F=5.45, 6.94, both P<0.05). The sEPSC frequency and quantification in the CUMS+ Veh group were lower than those in the CTRL+ Veh group (both P<0.01), and the sEPSC frequency and quantification in CUMS+ GBE group were higher than those of CUMS+ Veh group (both P<0.05). The interaction of GBE×CUMS of frequency and quantification of sIPSC in the four groups were significant ( F=7.78, 8.96, both P<0.01). The sIPSC frequency and quantification of the CUMS+ Veh group were higher than those of CTRL+ Veh group (both P<0.01), and the above indexes of CUMS+ GBE group were lower than those of CUMS+ Veh group (both P<0.01). As for the sEPSC/sIPSC ratio, GBE×CUMS interaction was significant ( F=5.45, P=0.02). The sEPSC/sIPSC ratio of CUMS+ Veh group (0.09±0.01) was lower than that of CTRL+ Veh group (0.28±0.04) ( P<0.01), and the sEPSC/sIPSC ratio of CUMS+ GBE group (0.14±0.03) was higher than that of CUMS+ Veh group ( P<0.05). Conclusion:Ginkgo biloba extract can improve the depression-like behavior of mice induced by CUMS, reduce the oxidative stress of mPFC and improve the excitation/inhibition balance of pyramidal neurons in depressive model mice.
ABSTRACT
Objective To evaluate the clinical efficacy of different combinations with "Shugan Jianpi" acupuncture and Yintang acupoint magnetic stimulation in the treatment of depression with liver depression and spleen deficiency type.Methods 160 patients with depression treated in hospital from December 2013 to June 2017 were divided into 4 groups according to the random number table,with 40 cases in each group.Group A received basic drug therapy," Shugan Jianpi" acupuncture combined with Yintang acupoint magnetic stimulation,group B received basic drug therapy combined with Yintang acupoint magnetic stimulation,group C received basic drug therapy combined with " Shugan Jianpi" acupuncture treatment,group D was treated with basic medicine only for 4 weeks.Hamilton Depression Scale (HAMD) was used to assess the short-term and long-term efficacy for 4 groups before treatment,after 2 weeks of treatment,after 4 weeks and 2 months after treatment and the safety of these 4 types of therapy was evaluated with the side effects scale (TESS).2 months after the treatment,the quality of life universal scale (SF-36) was evaluated for patients in 4 groups.Results After 2 weeks,4 weeks and 2 months of treatment,HAMD scores in the 4 groups were significantly lower than those before treatment (P＜0.05).After 2 weeks of treatment,HAMD score of A group was (15.28±3.45),and HAMD score of B,C,D group were ((18.30±3.57),(22.50±3.71),(27.30±4.82)) respectively.HAMD score of A group was significantly lower than those of B,C,D group (P＜0.05).After 4 weeks of treatment,HAMD scores in A,B group were significantly lower than those in C,D group (P ＜0.05).After 2 months of treatment,HAMD scores in all the 4 groups were further declined compared with those after 4 weeks of treatment (P＜ 0.05),however,there was no significant difference between the four groups (P＞0.05).The scores of each dimension of SF-36 in group A were significantly higher than those of group B,C and D (P＜0.05),and which in group B and C were significantly higher than those in D group after 2 months of treatment.(P＜0.05).There was no statistical difference among the 4 groups in TESS scores (P ＞0.05).Conclusion The results suggest that there is a synergistic effect in combination of the " ShuganJianpi" acupuncture combined with Yintang acupoint magnetic stimulation in the treatment of depression of liver qi stagnation and spleen deficiency type,and it can effectively reduce the degree and improve their quality of life in patients with depression.