盐皮质激素受体和糖皮质激素受体在创伤后应激障碍大鼠海马CA1区的共存表达

Co-expression of mineralocorticoid receptor and glucocorticoid receptor in hippocampal CA1 in posttraumatic stress disorder rats

目的:研究创伤后应激障碍(PTSD)大鼠海马CA1区神经元盐皮质激素受体(MR)和糖皮质激素受体(GR)表达及共存变化。方法:用连续单一刺激(SPS)方法刺激大鼠制作PTSD模型,用ELISA检测不同时间大鼠血清糖皮质激素(GC)。取SPS后12 h、1 d、7 d鼠脑组织,以非刺激的脑组织为对照组,用免疫荧光双标技术进行各组海马CA1区神经元MR和GR表达及二者共存表达的观察。结果:大鼠血清GC于SPS后1 h时明显增高,12 h时仍持续升高,24 h时低于正常,7、14 d回升但低于正常;激光共聚焦显微镜(CLSM)下,MR-CY3呈红光,GR-FITC呈绿光,二者融合为黄色或橙色光。对照组可见MR分布于胞质和胞核,GR主要分布于胞核,少数于胞质;12 h时MR表达减少,GR在胞核内明显增多;1 d时MR表达进一步减少且集中于胞质,GR集中于胞质;7 d时MR持续减少,GR重新表达于胞核。用双重波长激发时,对照组融合光集中于胞核,12 h时核内融合光增多,1 d时融合光集中于胞质,7 d时核内融合光再次增多。结论:MR、GR在海马CA1区神经元内表达与PTSD大鼠血中GC浓度变化相互影响,而导致海马受损、功能降低。

Objective To explore the expressions of mineralocorticoid receptor （MR） and glucocorticoid receptor （GR） and the change of their coexistence in hippocampal CA1 in posttraumatic stress disorder （PTSD） rats. Methods A rat model of PTSD was established with the single prolonged stress （SPS）-method. Serum glucocorticoid hormones （GC） was detected by ELISA at different time points. The brain tissues in rats 12 h and 1 and 7 days after treatment with SPS and the normal brain tissues used as control were collected. The expressions of MR and GR and their co-expression in the hippocampal CA1 in each group were observed by the double immunofluorescent labeling technology. Results After SPS treatment, serum GC significantly increased at hour one, still elevated at hour 12, declined to below normal at hour 24, and rebounded but lowered than normal at days 7 and 14. Under CLSM, MR-CY3 was red, GR-FITC was green, and the fusion light was yellow or orange. In the control group, MR distributed in the cytoplasm and the nucleus, GR mainly distributed in the nucleus, and some were in the cytoplasm. MR expression decreased and GR expression increased significantly in the nucleus at hour 12; the expression of MR further reduced and the expression of GR concentrated in the cytoplasm at day one ; the expression of MR continued to decrease and GR re-expressed in the nucleus at day 7. With dual wavelength excitation, the fusion light concentrated in the nucleus and increased at hour 12 in the control group, and the fusion light focused in the cytoplasm at day one but increased again in the nucleus at day 7. Conclusions The expressions of MR and GR in hippocampai CA1 interact with the changes of serum GC concentration in PTSD rat, resulting in hippocampal damage and a reduction in function.