百事乐胶囊对抑郁模型大鼠海马GR/p-GR/SGK1表达的影响

目的：探讨百事乐胶囊对慢性应激抑郁模型大鼠学习记忆的保护作用。方法：将SD大鼠随机分为6组，即空白对照组、抑郁模型组、氟西汀组及百事乐胶囊高、中、低（2.88，1.44，0.72 g·kg^-1）剂量组，采用慢性温和不可预见性应激加孤养的方法建立抑郁模型，造模同时灌胃给药，连续21 d Morris水迷宫测定对大鼠行为学的影响，放射免疫法观察大鼠血浆CORT含量的变化，Western-blotting观察大鼠海马GR，p-GR，SGK1蛋白表达的变化。结果：与空白对照组比较，模型组大鼠逃避潜伏期（EL）、目标象限潜伏时间显著增长（P<0.01）；穿越目标象限的次数显著降低（P<0.05）；CORT含量显著增高（P<0.01），海马GR、p-GR的表达下调（P<0.01），SGK1的表达增加（P<0.01）。与模型组比较，百事乐胶囊高剂量能缩短模型大鼠的EL（P<0.05），并能缩短目标象限潜伏时间（P<0.05），增加目标象限的穿越次数（P<0.05）；同时高、中剂量组大鼠血浆CORT的含量显著下降（P<0.05或P<0.01）；高、中剂量组海马GR、p-GR的表达显著增加（P<0.05或P<0.01），高剂量组SGK1的表达显著降低（P<0.05）。结论：百事乐胶囊可能通过GR/p-GR/SGK1信号级联增加应激抑郁模型大鼠海马学习记忆的功能，进而实现抗抑郁的作用。

Effects of Baishile Capsules on GR/p-GR/SGK1 expression in hippocampus of depression rat model

OBJECTIVE To study the protective effects of Baishile Capsules on learning and memory functions in depressive rats induced by chronic stress.METHODS SD rats were randomly divided into six groups,including the groups of control,model,fluoxetine,high,medium and low (2.88,1.44,0.72 g·kg^-1) doses of Baishile capsules.Chronic unpredictable mild stress combined with single housing was used to established the model of depression,and the drugs were intragastrically administered,which lasted for 21 days.Morris water maze was used to measure behaviors of rats,and radioimmunoassay was used to detect CORT content in rat plasma.Western blotting was used to detect the protein levels of GR,p-GR,SGK1 in hippocampus in each group.RESULTS Compared with control group,the time of escape latency (EL) and target quadrant latency increased significantly (P<0.01),the time of crossing target decreased significantly (P<0.05); the content of CORT increased (P<0.01); expression levels of GR and p-GR decreased (P<0.01); level of SGK1 increased (P<0.05).Compared with model group,high dose of Baishile capsule reduced time of EL (P<0.05) and shortened target quadrant latency (P<0.05),increased the time of crossing target (P<0.05).Meanwhile,high and medium doses of Baishile capsules significantly decreased the content of CORT in rat plasma (P<0.05),high dose of Baishile capsules obviously increased expression levels of GR and p-GR (P<0.05 or P<0.01),and reduced level of SGK1 (P<0.05).CONCLUSION Baishile capsules can obviously improve learning and memory functions in depressive rats,which might be associated with the promotion of GR/p-GR/SGK1 signaling cascade,and then exert antidepressant effects.