Intervention Effect of Zishui Qinggan (滋水清肝)Decoction on Depression Model of Mice with Corticosterone Replacing Drinking Water Based on JAK2/ERK1/2/STAT3 Signaling Pathway
Objective:To investigate the intervention effect of Zishui Qinggan(滋水清肝) Decoction on the depression model of mice with corticos-terone (CORT) replacing drinking water through the Januskinase 2 (JAK2)/Extracellular regulated kinase 1/2 (ERK1/2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway.Methods:Except for the normal control group,CORT was used to replace drink-ing water to establish a depression model of mice.After 21 days of modeling,the mice were randomly divided into five groups according to the sucrose preference results:model group,fluoxetine hydrochloride group (0.01 g/kg),and Zishui Qinggan Decoction groups (8.84 g/kg,17.67 g/kg and 35.34 g/kg).Fluoxetine hydrochloride and Zishui Qinggan Decoction groups were administrated intragastricly for 14 days,respectively.The sucrose preference test and the behavioral test were performed after weekly administration.The hematoxylin-eosin (HE) staining was used to observe the morphological changes in the hippocampus of mice.The fluorescence intensity of ionized calcium binding a-dapter molecule-1 (Iba-1) was detected by immunofluorescence staining,and its quantity was counted.The contents of malonaldehyde (MDA),5-hydroxytryptamine (5-HT),noradrenaline (NA),and CORT in the serum and hippocampus of mice were detected.The mRNA expressions of tumor necrosis factor-α(Tnf-α) and Interleukin 1β (Il1β) in hippocampus of mice were determined by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR),and the protein expressions of JAK2,p-JAK2,ERK1/2,p-ERK1/2,STAT3,and p-STAT3 in hippocampus of mice were determined by Western blotting (WB).Results:Compared with the normal control group,the sucrose preference rate of the model control group decreased,and the immobility time was prolonged.The movement distance,movement time,and average speed decreased,and the peripheral dwell time was prolonged.The nerve cells in the hippocampus were deformed and blurred in outline.The fluo-rescence intensity and quantity of Iba-1 in the DG region of the hippocampus were increased.The levels of 5-HT and NA in serum and hippo-campus were decreased,and the contents of MDA and CORT were increased.The mRNA expressions of Tnfα and Il1β in the hippocampus of mice were increased,and the protein expressions of p-JAK2 and p-STAT3 were increased.The protein expression of p-ERK1/2 was decreased (P<0.05 or P<0.01).Compared with the model control group,the sucrose preference rate of mice in each administration group increased,and the immobility time shortened.The movement distance,movement time,and average speed increased,and the peripheral dwell time was reduced.The nerve cells were improved,and the shape returned to normal.The fluorescence intensity and quantity of Iba-1 in the DG region of the hippocampus decreased.The levels of 5-HT and NA in serum and hippocampus were increased,while the contents of MDA and CORT were decreased.The mRNA expressions of Tnfα and Il1β in the hippocampus of mice were decreased,and the protein expressions of p-JAK2 and p-STAT3 were decreased.The protein expression of p-ERk1/2 was increased.The Zishui Qinggan Decoction group of 17.67 g/kg showed the most significant difference (P<0.05,P<0.01).Conclusion:Zishui Qinggan Decoction can significantly improve depression-like behavior,reduce inflammation,and alleviate HPA axis disorder in mice with CORT replacing drinking water,and its mechanism may be related to the regulation of the JAK2/ERK1/2/STAT3 signaling pathway in the hippocampus of mice.
Zishui Qinggan (滋水清肝) DecoctionDepressionModel with CORT Replacing Drinking WaterJanuskinase2 (JAK2)/Extracellular-regulated kinase 1/2 (ERK1/2)/Signal transducer and activator of transcription 3 (STAT3) Signaling Pathway
NETL
NSTL
万方数据
