| ObjectiveIn order to investigate the effects of Guiluerxianjiao(GLEXJ)on the changes of behaviors and hypothalamic-pituitaiy-adrenal(HPA)axis function in a rat model of post-traumatic stress disorder(PTSD)and further explore the mechanism of GLEXJ.Methods(1)Single prolonged stress(SPS)was used to establish the rat model of PTSD.(2)Open field test(OFT)and elevated plus maze test(EPMT)were used to assess the levels of locomotor activities and anxiety behaviors dynamically(3)In the dexamethasone suppression test(DST),plasma ACTH levels measured by ELISA.(4)The plasma corticosterone(CORT)and corticotropin-releasing hormone(CRH)levels in rats were detected by ELISA.(5)The contents of GR mRNA,MR mRNA,CRF1R mRNA and CRF2R mRNA in the hippocampus and amygdala were determined by RT-PCR.(6)Immunohistochemistry was used to detect the expression of GR,MR,CRF1R and CRF2R at protein level in the hippocampus and amygdala.Results(1)PTSD rats appeared behavioral changes in day 9 after SPS,and these changes still existed at day 29 and day 30 after SPS.EPMT result shown that compared with the control group,percentage of entries in open arms significantly reduced on day 9 in SPS group(P<0.05),and percentage of time,distance and entries in open arms significantly decreased both on day 23 and d 30 in SPS group(P>0.05).Compared with the control group,total distance of SPS group in OFT significantly declined on day 29(P<0.05).Total distance in OFT and percentage of entries in open arms in EPMT was significantly increased after 21 days treated by GLEXJ(P<0.05).(2)On day 8,day 22 and day 29 after SPS,SPS group had a significantly lower levels of plasma ACTH than control group(P<0.05).Plasma ACTH levels in GLEXJ group were significantly increased compared with that of the SPS group after treated 14 and 21 days(P<0.05).(3)Plasma CORT levels of PTSD rats showed a gradually increasing trend from day 8 to day 29,and was significantly increased in day 29 compared with control group(P<0.05).Plasma ACTH levels in GLEXJ group were significantly decreased after treated 21 days(P<0.05).While the levels of CRH in plasma were no significant change at three time points and group(P>0.05).(4)The expression of GR mRNA?MR mRNA?CRF1R mRNA in the hippocampus of the SPS group were significantly increased and CRF2R mRNA was significantly decreased in day 29 after SPS(P<0.05).The expression of MR mRNA and CRF2R mRNA in the amygdala of the SPS group were significantly decreased(P<0.05)while GR mRNA and CRF1R mRNA were no significant difference with control group in day 29 after SPS(P>0.05).After 21 days treatment,GLEXJ group significantly decreased the expression of GR mRNA,MR mRNA,CRF1R mRNA and increased the expression of CRF2R mRNA in the hippocampus as well as increased the expression of CRF2R mRNA in the amygdala(P<0.05).The expression of MR mRNA,CRF1R mRNA and GR mRNA in the amygdala had no statistical difference in GLEXJ group(P>0.05).(5)Compared with control group the expression of GR and MR protein in the hippocampus of the SPS group significantly increased(P<0.05)while CRF1R and CRF2R had no statistical difference(P>0.05).The expression of GR,MR and CRF1R protein in the amygdala of the SPS group significantly decreased(P<0.05)while CRF2R had no statistical difference compared with control group(P>0.05).After 21 days treatment,the expression of GR and MR protein in hippocampus significantly decreased(P<0.05)and the expression of GR,MR and CRF1R protein in the amygdala significantly increased in GLEXJ group(P<0.05).CRF1R and CRF2R in the hippocampus and CRF2R in the amygdala had no statistical difference in GLEXJ group(P>0.05).Conclusion(1)PTSD rat began to appear persistent anxiety-like behaviors in day 9 after SPS,and locomotor activity decreased significantly on day 29.After 21 days of continuous administration,GLEXJ significantly attenuated the anxiety-like behaviors and increased the locomotor activity induced by SPS.(2)PTSD rat began to appear enhanced HPA axis negative feedback function in day 9 and persistent exist till to day 29 after SPS.Basic CORT level significantly increased in day 29.After 14 days of continuous administration,GLEXJ significantly inhibited enhanced HPA axis negative feedback,after 21 days of continuous administration,GLEXJ not only significantly inhibited enhanced HPA axis negative feedback but also decreased plasma CORT levels.(3)GLEXJ could significantly attenuated behaviors disorder and regulated HPA axis negative feedback which may be related to regulate the expression of GR,MR,and CRP1R in the hippocampus and amygdala. |
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