百合知母汤对抑郁症大鼠环磷酸腺苷信号通路的影响

Effect of Baihe Zhimu Decoction on cAMP Signal Transduction Pathway of Depression Rats

目的:观测百合知母汤对抑郁症大鼠学习记忆功能的影响,探讨其环磷酸腺苷信号转导机制。方法:将50只SD大鼠随机分成正常对照组、模型组、氟西汀组、百合知母汤高、中剂量组5组;除正常组外,其余4组采用慢性温和不可预见刺激结合孤养制造抑郁症模型,共49d;于第22天各组动物分别灌胃生理盐水、氟西汀及百合知母汤高、中剂量,共计28d;于第50天采用Morris水迷宫法分别进行定位航行及空间探索实验,分别测定大鼠逃避潜伏期、穿越第4象限时间、路程、第一次穿越时间、穿越次数等;ELISA法、Western-blot、qPCR法分别测定大鼠海马组织环磷酸腺苷(cAMP)、蛋白激酶A(PKA)、cAMP反应元件结合蛋白(CREB)的含量。结果:与模型组比较,百合知母汤高、中剂量组大鼠逃避潜伏期、穿越第4象限时间路程、第一次穿越时间均降低,穿越次数升高(P<0.05,0.01);海马cAMP、PKA、CREB的含量提高(P<0.05,0.01)。结论:百合知母汤能改善抑郁症大鼠学习记忆功能,其机制可能与激活cAMP-PKA-CREB信号转导通路有关。

Objective：To explore the effect of Baihe Zhimu decoction,a traditiona Chinese medicine,on learning and memory of depression rats whether through the cAMP-PKA-CREB pathway.Methods：Fifty SD rats were devided into five groups randomly as control group,model group,Fluoxetine group,high and moderate dosage of Baihe Zhimu decoction group.Firstly,the depression models were established by using unpredictable chronic mild stimulation combined with isolated keeping for 49 days.All rats were given either of saline,Fluoxetine or Baihe Zhimu decoction respectively for 28 days.Place navigation and space exploration test were done on the49 th day by means of Morris water maze,in which escape latency（EL）,time and length crossing（TC,LC）,the 4th quadrant（QT）,total times（TT）,and the 1st through time（FTT）were measured.Then the changes of cAMP and PKA in the hippocampus of rats were tested through ELISA and Western-blot respectively.Results：As compared with that in model group respective-ly,EL,TC,LC,and QT of high dosage group and moderate dosage group were decreased and TT was increased.The cAMP,PKA,and CREB in the hippocampus were also increased in both high dosage group,moderate dosage group,and Fluoxetine group.Conclusion：Baihe Zhimu decoction could improve the learning and memory of depression rats via the way of cAMP-PKACREB signal transduction.1 Basic Medical College of Hubei University of Chinese Medicine, Wuhan 430065, China Hubei University of Chinese Medicine, Wuhan 430065, China