Effect of Suanzaoren Decoction on behavior and JAK2/STAT3 and ERK/CREB signaling pathways in PTSD model mice
Objective To explore effects and mechanisms of Suanzaoren Decoction on behavior of mice with post-traumatic stress disorder(PTSD)model.Methods Except for the control group,the rest of the mice were subjected to a single prolonged stress and foot shock(SPS&S)to establish the PTSD model.After the model was established,the mice were randomly divided into five groups:model group and Suanzaoren Decoction low,medium,and high dose(3,6,and 12 g·kg-1)groups and paroxetine hydrochloride(0.01 g·kg-1),with eight mice in each group.The control group and the model group were given an equal volume of distilled water,and the mice in each group were administered with the respective treatments by ig for 14 consecutive days.After the last delivery,behavioral tests,hematoxylin-eosin(HE)staining were used to observe the mice hippocampal tissue pathological changes;Immunofluorescence staining was used to detect the fluorescence intensity of hippocampal microglia marker Iba-1;ELISA method was used to detect the mice serum TNF-α,IL-6,CORT and TNF-α,IL-6,CORT,5-HT,BDNF levels in the hippocampus;The protein expressions of JAK2,p-JAK2,STAT3,p-STAT3,ERK1/2,p-ERK1/2,CREB and p-CREB in hippocampus were detected by Western blotting.Results Compared with the blank group,the mice in the model group showed significantly prolonged stagnation time in the fear extinction test(P＜0.01),significantly reduced distance and retention time in the central area of the open field test(P＜0.01),significantly shortened number of entry into the open arm and residence time in the elevated plus maze test(P＜0.01),and significantly increased forced swimming immobility time(P＜0.01).Tip model preparation of success.The hippocampal neurons were obviously damaged,the fluorescence intensity of Iba-1 in CA1 region of hippocampus was increased.The contents of serum TNF-α,IL-6 and CORT in the mice were significantly increased(P＜0.05,0.01),and the contents of hippocampal TNF-α,IL-6 and CORT were significantly increased(P＜0.05),while the contents of 5-HT and BDNF were significantly decreased(P＜0.05,0.01).p-JAK2,p-STAT3 protein expression was significantly increased(P＜0.05),p-ERK1/2,p-CREB protein expression decreased significantly(P＜0.05);Compared with model group,Suanzaoren Decoction and paroxetine hydrochloride after treatment could obviously improve the behavior(P＜0.05,0.01),improve hippocampal neurons in mice,decrease the fluorescence intensity of Iba-1 in CA1 region of hippocampus,decrease the levels of TNF-α,IL-6 and CORT in serum(P＜0.05,0.01),and increase the levels of 5-HT and BDNF in hippocampus(P＜0.05,0.01),reduce p-JAK2,p-STAT3 protein expression significantly(P＜0.05,0.01),increase p-ERK1/2,p-CREB protein expression significantly(P＜0.05,0.01).Conclusion Suanzaoren Decoction can significantly improve the fear,anxiety,and depression-like behaviors of PTSD mice,and its mechanism may be related to regulating the JAK2/STAT3,ERK1/2/CREB pathways,improve nerve inflammation,adjusting HPA axis disorders,increase content of 5-HT,BDNF.
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