Therapeutic Effect and Mechanism of Yigan Powder on Apoptosis of Hippocampal Neurons in Mice with Post-traumatic Stress Disorder
Objective To investigate the effects of Yigan Powder on the behavior and neuronal apoptosis of post-traumatic stress disorder(PTSD)mice,and to analyze its mechanism of action through cyclic adenosine monophosphate response element-binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway.Methods A to-tal of 58 male C57BL/6J mice were selected and randomly divided into normal group(do not build model+giving volume normal saline lavage,n=12),model group(PTSD modeling+giving volume normal saline lavage,n=10),low-dose Yigan Powder group[PTSD modeling+giving 0.5 g/(kg·d)Yigan Powder by gavage,n=12),high-dose Yigan Powder group[PTSD modeling+giving 1 g/(kg·d)Yigan Powder by gavage]and sertoline hydro-chloride group[PTSD modeling+giving 0.01 g/(kg·d)sertoline hydrochloride by gavage,n=12].The behavioral changes of the mice were evaluated by open field test,trauma cue avoidance test and contextual fear test;the pathological changes of hippocampal cells in mice were observed by Nissl staining;the apoptosis of hippocampal tissue cells in mice was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL);the protein levels of BDNF,phosphorylated CREB(p-CREB)and tyrosine kinase receptor B(TrkB)in hippocampal tissues of mice were de-tected by Western blot.Results Compared with the normal group,the model group showed a significant decrease in the percentage of central zone movement distance and exploration object time and an significant increase in cataleptic time(all P＜0.05),the hippocampal tissue cells showed structural abnormalities and necrosis;the number of apoptotic hippocam-pal neurons increased(P＜0.05);and the protein expression levels of TrkB,BDNF and p-CREB in the hippocampal tis-sues significantly decreased(P＜0.01).After administration,compared with the model group,the low-dose Yigan Pow-der group,high-dose Yigan Powder group and the sertoline hydrochloride group showed an increase in the percentage of central zone movement distance in the open field test(all P＜0.05),the low-dose Yigan Powder group showed an increase in exploration object time(P＜0.05),and the high-dose Yigan Powder group showed a decrease in cataleptic time(P＜0.05);compared with the model group,the low-dose Yigan Powder group,high-dose Yigan Powder group and the serto-line hydrochloride group showed alleviation of hippocampal tissue cell structural abnormalities and necrosis,the high-dose Yigan Powder group and the sertoline hydrochloride group showed a decrease in the number of apoptotic hippocampal neu-rons(P＜0.01);compared with the model group,the low-dose Yigan Powder group,high-dose Yigan Powder group and the sertoline hydrochloride group showed an increase in protein expression levels of TrkB,p-CREB and BDNF in hipp-ocampal tissues(all P＜0.01).Conclusion Yigan Powder can activate CREB/BDNF signaling pathway,inhibit neuronal apoptosis in PTSD mice,and improve anxiety,active avoidance behavior and re-experience behavior in mice.
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