加味温胆汤对抑郁模型大鼠海马钙调蛋白激酶与丝裂原活化蛋白激酶信号转导通路的影响

Effect of Jiawei Wendan decoction regulating CaMK/MAPK signal pathway in hippocampus of depression model rats

目的探讨加味温胆汤对抑郁模型大鼠海马钙调蛋白激酶（CaMK）通路、丝裂原活化蛋白激酶（MAPK）通路的整体调节作用。方法以孤养结合慢性不可预见性应激抑郁模型大鼠为研究对象，在CaMK、MAPK信号转导通路上关键因子mRNA/蛋白表达及信号通路交汇点CREB1mRNA表达检测的基础上，采用相关分析方法，探讨CaMK、MAPK级联信号转导通路上关键因子CaMK II、RSK蛋白与信号通路交汇点CREB1mRNA的相关性。结果①双向相关分析：模型组、中药组、西药组大鼠海马CaMKⅡ蛋白与CREB1mRNA表达的相关系数分别为r=-0．502（P〈0．01），r=-0．643，（P〈0．01），r=-0．408（P〈0．05）；模型组、中药组、西药组人鼠海马RSK蛋白与CREB1mRNA表达的相关系数分别为r=0．550（P〈0．01），r=0．687（P〈0．01），r=0．407（p〈0．01）。②回归分析（强行投入法）：模型组、中药组、西药组大鼠海马CaMK II蛋白（负向）和RSK（正向）与CREB1 mRNA表达的回归系数分别为：R2=0．472，F=12．983（P〈0．01），R2=0．666，F=28．961（P〈0．01），R2=0．356，F=8．004（P〈0．01）。结论加味温胆汤可通过整体调节CaMK、MAPK信号转导通路，进而上调CREB1mRNA表达发挥抗抑郁效应。

Objective To explore the effect of Jiawei Wendan decoction on whole regulating function of CaMK/MAPK signal pathway in hippoeampus of depression model rats. Methods Isolated depression model rats as research object were living unpredictable chronic stress. Based on the examination of mRNA/protein expression which was the key factor of the signal pathway of CaMK/MAPK and the intersection CREBhnRNA expression, the relationship between CaMK II/RSK protein expression and the CREBI mRNA expression were analyzed with relation analysis method. Results （1） Bidirectional correlation analysis： the respective coefficient （r value） of CaMK II protein expression and the CREBImRNA expression in hippocampus of the model group,Chinese medicine treatment group and western medicine treatment group were - 0. 502 （P 〈 0.01 ）, - 0. 643 （P 〈 0.01 ）, -0. 408 （P 〈 0.05 ） ;the respective coefficient（ r value） of RSK protein expression and the CREB1 mRNA expression in hippoeampus of the model group, Chinese medicine treatment group and western medicine treatment group were 0. 550 （P 〈 0.01 ） , 0. 687 （P 〈 0.01 ） ,0. 407 （P 〈 0.01 ）.（2）Regression analysis ： the respective regression coefficient of CaMK II protein （positive direction）, RSK protein （negative direction） and CREB1 mRNA expression in the model group, Chinese medicine treatment group and western medicine treatment group were R 2 = 0. 472, F = 12.983（P〈0.01）,R2 = 0. 666 , F= 28. 961（P 〈 0. 01） , R2=0.356,F=8.004（P〈0.01）. Conclusion The anti-depressant effecl mechanism of Jiawei Wendan decoction is to regulate the whole function of the CaMK and MAPK signal pathway and then further up-regulate CREB1 mRNA expression.