越鞠丸醇提物调控PKA信号改善强迫游泳应激小鼠学习记忆障碍及抑郁样行为

Yueju Pill Alcohol Extract Regulates Recognition Memory and Antidepressant-Like Activities via PKA Signaling in Stressed Mice

目的：分析越鞠丸醇（YJ）对强迫游泳应激小鼠学习记忆障碍及抑郁样行为的影响。方法：将小鼠随机分成无应激＋溶媒组（NS＋Veh）、应激＋溶媒组（FS＋Veh）以及应激＋YJ组（FS＋YJ）暴露于连续两天的强迫游泳应激,应激结束后20 min,3组小鼠进行NOR测试。观察YJ对小鼠的自发活动。随后将小鼠分为应激＋溶媒组（FS＋Veh）、应激＋NBQX组（FS＋NBQX）、应激＋YJ组（FS＋YJ）和应激＋NBQX＋YJ组（FS＋NBQX＋YJ）。4组小鼠经历FS应激程序和NOR测试,观察小鼠KA受体抑制剂H89阻断以及AMPA受体抑制剂NBQX对YJ改善强迫游泳应激小鼠学习记忆障碍及抑郁样行为的影响。结果：应激＋YJ组小鼠不动时间显著性低于应激＋溶媒组（P〈0.01）,各组小鼠在两物体上的总探索时间存在显著性差异（F=4.139,P﹤0.05）,各组DI存在显著性差异（F=8.086,P﹤0.01）,FS＋Veh组小鼠辨别指数显著性低于NS＋Veh组（P〈0.01）,FS＋YJ组小鼠辨别指数显著性高于FS＋Veh组（P〈0.01）。此外,H89逆转YJ对强迫游泳应激诱导小鼠NOR中学习记忆损伤的改善作用;NBQX对YJ改善强迫游泳应激小鼠NOR中学习记忆损伤没有影响。结论：研究表明在FSS应激小鼠中YJ发挥抗抑郁样作用和学习记忆改善作用,并且YJ的这种作用依赖于PKA信号,而不依赖于AMPA受体。

Objective： To analyze Yueju alcohol extract（ YJ） on effects of forced swimming stress on learning and memory disorder and depressive-like behavior in mice. Methods： Mice were randomly divided into non stress ＋ vehicle group（ NS ＋ Veh）,solvent group（ FS ＋ ＋ stress Veh） and stress group ＋ YJ（ FS ＋ YJ）,exposing to two consecutive days of forced swimming stress. 20 min after finishing the stress,three groups＇ mice were tested by NOR. We observed the spontaneous activity of YJ in mice. And then the mice were divided into three groups： stress ＋ solvent group（ FS ＋ Veh）,stress＋ NBQX group（ FS ＋ NBQX）,stress ＋ YJ group（ FS ＋ YJ） and stress ＋ NBQX ＋ YJ group（ FS ＋ NBQX ＋）. Four groups＇ mice were exposed to FS stress test and NOR test to observe the effects of KA receptor inhibitor H89 and AMPA inhibitor NBQX on learning and memory impairment and depression like behaviors in mice induced by forced swimming stress（ YJ）. Results： The stress of YJ group was significantly lower than that of the real time stress ＋ vehicle group（ P 0. 01） and there was significant difference between the total exploration time in two on the object of mice（ F = 4. 139,P 0. 05）. There was significant difference between the groups of DI（ F = 8. 086,P 0. 01）. FS ＋ Veh group＇s distinguishing index significantly lower than was that of NS ＋ Veh group（ P 0. 01）. FS ＋ YJ group＇s distinguishing index was significantly higher than that of the FS ＋ Veh group（ P 0. 01）. In addition,H89 reversed the effect of YJ on the learning and memory impairment induced by forced swimming stress in NOR mice and NBQX had no effect on the improvement of learning and memory impairment in NOR mice induced by forced swimming stress（ YJ）. Conclusion： YJ has been shown to exert antidepressant-like effects and improve learning and memory in FSS stressed mice and the effect of YJ is dependent on PKA signaling,but not on AMPA receptors.