Effect and mechanism of Guilu Erxian Jiao on negative feedback function of HPA axis in rats with post-traumatic stress disorder / 中华行为医学与脑科学杂志

ABSTRACT

Objective:To investigate the effect of Guilu Erxian Jiao (GEJ) on the negative feedback function of hypothalamic-pituitary-adrenal (HPA) axis and its possible mechanism in rats with post-traumatic stress disorder(PTSD).Methods:The PTSD rat model was established using single prolonged stress (SPS). Ninety six SD rats were randomly divided into control group (control), model group (SPS), GEJ group (GEJ) and paroxetine group (PRX) according to the random number table with 24 rats in each group. Except the control group, the rats in the other groups were constructed using the PTSD model. On the 8th day after the establishment of the model, the rats of the GEJ group (3.6 g/kg) and the PRX group (10 mg/kg) were respectively given the drug by gavage for 21 days. The rats in control group and SPS group were given the same amount of distilled water once a day for 21 days. After continuous administration for 21 days, 12 rats were randomly selected from each group for the dexamethasone suppression test (DST), then 6 rats were selected for the RT-PCR, and the remaining 6 rats were used for immunohistochemistry. The contents of plasma adrenocorticotrophic hormone (ACTH) were measured by Elisa. The expression levels of glucocorticoid receptor (GR), mineralocorticoid receptor (MR), adrenocorticotropic hormone releasing factor Ⅰ receptor (CRF1R) and adrenocorticotropic hormone releasing factor Ⅱ receptor (CRF2R) were detected by RT-PCR and immunohistochemistry.Results:(1) In DST, plasma ACTH level in SPS group was significantly lower than that in control group((145.89±19.41)μg/L, (203.59±35.78)μg/L, t=3.16, P<0.01), and that in the PRX group and GEJ group were significantly higher than that in SPS group((218.47±37.55)μg/L, t=3.98, P<0.01; (205.33±66.54)μg/L, t=3.26, P<0.01). (2) RT-PCR results showed that, in hippocampus, the GR mRNA and MR mRNA expressions in SPS group were significantly higher than those in control group((1.29±0.02), (1.00±0.06), t=6.88, P<0.01; (1.38±0.02), (1.00±0.05), t=7.97, P<0.01), and that in the GEJ group significantly decreased comparing to SPS group((0.96±0.07), t=7.87, P<0.01; (0.86±0.13), t=11.03, P<0.01). (3) Immunohistochemical results showed that, in hippocampus, the positive cell expressions of GR and MR in the SPS group were significantly higher than those in control group((84.33±12.82), (69.33±8.19), t=2.50, P<0.05; (77.33±6.65), (56.33±11.79), t=2.25, P<0.05), and that in the GEJ group significantly were lower than SPS group((68.33±4.55), t=2.67, P<0.05; (59.50±4.18), t=2.25, P<0.05). In amygdala, the positive cells expression of GR, MR and CRF1R in the SPS group significantly decreased compared with the control group((62.67±6.89), (77.17±10.70), t=3.10, P<0.05; (60.50±11.66), (91.83±15.63), t=3.43, P<0.05; (54.50±19.96), (88.17±22.43), t=2.31, P<0.05); and that in GEJ group significantly increased compared with the SPS group((74.33±5.85), t=2.11, P<0.05; (83.67±12.55), t=2.53, P<0.05; (88.67±16.28), t=2.35, P<0.05). Conclusion:GEJ can inhibit the enhanced HPA axis negative feedback function induced by SPS, which may be related to regulating expression of GR, MR and CRF1R in the hippocampus and amygdala.