右美托咪定和米非司酮对创伤后应激障碍大鼠恐惧记忆的影响及机制

Effect and mechanism of dexmedetomidine and mifepristone on fear memory in rats with PTSD

目的探讨右美托咪定、米非司酮及两者联合使用对PTSD模型大鼠恐惧记忆的影响及其机制。方法选取雄性SD大鼠40只，分为5组，分别为对照组（C组）、PTSD组（P组）、右美托咪定组（D组）、米非司酮组（M组）和右美托咪定、米非司酮联合使用组（U组），每组8只。通过条件性恐惧记忆实验（fear conditioning test，FC）测定大鼠的恐惧记忆，高架十字迷宫实验测定大鼠的焦虑状态，通过酶联免疫吸附法测定大鼠血清皮质酮（corticosterone，CORT）含量，免疫印迹法测定大鼠海马脑源性神经营养因子（brain derived neurotrophic factor，BDNF）及其特异性受体TrkB的水平。结果与P组比较，D组[（32．29±8．09）％]、M组[（33．33±8．21）％]、U组[（9．38±3．31）％]的恐惧记忆明显降低（P〈0．05）；焦虑样行为明显改善（P〈0．05）；D组（0．65±0．04）、M组（0．71±0．04）、U组（0．79±0．07）海马BDNF的表达上调（P〈0．05），D组（0．66±0．04）、M组（0．67±0．05）、U组（0．86±0．03）海马TrkB的表达也上调（P〈0．05）；D组[（37．65±12．37）μg/L]、U组[（59．10±5．23）μg/L]的血清CORT含量降低（P〈0．05），M组无明显变化。结论右美托咪定和米非司酮以及两者合用均可以促进PTSD大鼠恐惧记忆的消退，其机制可能与上调海马BDNF及其特异性受体TrkB的表达有关。

Objective To investigate the effect and mechanism of dexmedetomidine, mifepristone and dexmedetomidine plus mifepristone on the fear memory in rats with post-traumatic stress disorder （PTSD）. Methods 40 male SD rats were randomly divided into five groups with 8 in each group：control group （ group C）, PTSD model group （ group P ）, dexmedetomidine group （ group D ）, mifepristone group （ group M） and dexmedetomidine plus mifepristone group （ group U）. Fear memory in rats was evaluated by fear conditioning test （FC）. Anxiety-like behavior was assessed by the elevated plus-maze test （EPM）. Expressions of BDNF and its receptor TrkB in the hippocampus of rats after fear condition were detected using Western blot （WB） and CORT level in the serum was detected using enzyme-linked immunosorbent assay （ELISA）. Results Compared with group P,the freezing scores in the FC in group D（（32.29±8.09） %） , M （ （33.33±8.21 ） %） , and U （ （9.38±3.31 ） %） were significantly decreased （P〈0.05）. The times and entries in the open arms of the EPM were significantly increased （P〈0.05）. The expressions of BDNF in group D（0.65±0.04） ,M（0.71±0.04）,U（0.79±0.07） and TrkB in group D（0.66±0.04）,M（0.71±0.04）,U （0.86±0.03） were obviously rescued in hippoeampus of rats （P〈0.05）. The CORT level in serum in group D （（37.65±12.37）μg/L） and U（（59.10±5.23）μg/L） was decreased （P〈0.05）. There was no difference between group P and M. Conclusion These results suggest that dexmedetomidine, mifepristone and dexme- detomidine plus mifepristone can significantly enhance fear extinction and improve anxiety-like behaviors in rats with PTSD. The mechanism may be that dexmedetomidine and mifepristone could enhance the expressions of BDNF and TrkB in the hippocampus.