米非司酮改善不可预计性慢性应激所致大鼠学习和记忆功能损伤
Mifepristone improves impaired learning and memory function induced by unpredictable chronic stress in rats

摘要：目的 探索米非司酮对不可预计性慢性应激(UCS)所致大鼠学习和记忆损伤的保护作用。方法 雄性Wistar大鼠40只分为对照组、模型组、治疗组(分大、中、小剂量3组)，每组8只。对照组不给予特殊处理；模型组给予21d UCS；治疗组在给予UCS的同时，每天分别给予50、100、200mg/kg的米非司酮。处理前后分别做电迷宫和物体识别实验，检测血促肾上腺皮质激素(ACTH)、皮质酮(CORT)浓度。结果 处理前各组在电迷宫和物体识别实验中的指标无明显差异。处理后，模型组和小剂量治疗组的正确反应次数、辨别指数均明显降低且低于对照组(P<？？0.01？？)；大、中剂量组较前变化不明显但显著高于模型组(P<0.01)。模型组和小剂量治疗组的总反应时间明显延长且长于对照组，但大、中剂量治疗组总反应时间延长不明显且明显短于模型组(P<0.01)。处理前各组血ACTH和CORT浓度无明显差异，处理后模型组和各治疗组均明显升高(P<0.01)，且高于对照组(P<0.01)。结论 米非司酮可在一定程度上拮抗UCS所致的大鼠学习和记忆损伤，并呈现出剂量依赖性。
ABSTRACT: Objective To explore the effect of mifepristone on impaired learning and memory function induced by unpredictable chronic stress (UCS). Methods Male Wistar rats were randomly divided into control, model, and three treatment groups, with eight in each group. Control group received no special treatment, and model group was given UCS for 21 days. In addition to UCS, the three treatment groups were administered with 50, 100, and 200mg/kg of mifepristone daily. The concentrations of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were measured before and after processing. Meanwhile, the electric maze and object recognition experiments were conducted. Results All the indexes in electric maze and object recognition experiments had no obvious differences before administration among the groups. The number of correct reaction times and recognition index (RI) in model and small-dosage treatment groups obviously decreased (P<0.01), and were significantly lower than in control group (P<0.01) after processing, while those in medium- and large-dosage groups did not significantly change compared with those before processing but were significantly higher than in model group (P<0.01). The total reaction time in model and small-dosage groups significantly extended (P<0.01) and was longer than in control group (P<0.01) after processing, but the extension time was not obvious in medium- or large-dosage groups. Serum ACTH and CORT concentrations did not obviously differ among the three groups before processing, but they significantly increased after processing in model and treatment groups (P<0.01), and were also higher than in control group (P<0.01). Conclusion Mifepristone can improve UCS-induced impairment in learning and memory function in rats in a dose-dependent manner