Study On The Antidepressant Effect Mechanism Of JiaotaiPill And Its Separated Recipes Based On PI3K/AKT/mTOR Signaling Pathway

Objective:In this study,a chronic mild unpredictable stress(CUMS)method was used to establish a depression model.To observe the effects of Jiaotai Pill and its separated recipes and its use alone on coptis and cinnamon on the behavior of CUMS depressed rats,and the effects of key factors on the PI3K/AKT/m TOR signal pathway.The results were used to clarify the antidepressant mechanism of Jiaotai Pill,and to reveal the scientific connotation of Jiaotai Pill antidepressant effect.Methods:According to the initial body weight and the results of open field test results,the wistar male rats were randomly divided into nine groups: blank control group,model group,high and low dose group of Jiaotai Pill,high and low dose group of coptis,high and low dose group of cinnamon,positive drug group.The blank control group did not receive any stimuli,and the other groups received 35 days of chronic mild unpredictable stress,including ice-water swimming,day and night inversion,binding and restraint,tail clamping,shaking,fasting and water fasting.Animals in each group were randomly given a stimulus every day,and were treated with drugs separately on the 21 st day after stimulation.The depression model of rats was successfully established by CUMS method,Jiaotai Pill,coptis,cinnamon and fluoxetine were given by gavage continuously for two weeks according to the weight ratio of 1ml / 100 g.The blank group and the model group were given by gavage with the same amount of ultra pure water.At the same time,they were continuously stimulated.To observe the weight change of rats every week,to detect the 1% sugar water preference rate of rats to observe the loss of interest pleasure,and to observe the open field experiment(horizontal distance and standing times)to reflect the autonomous behavior of rats.After animal experiments,Western Blotting was used to detect rat hippocampal tissue protein and its phosphorylated protein expression levels: phosphatidyl inositol 3 kinase(PI3K),protein kinase B(AKT),mammalian target of rapamycin(m TOR),and e IF4E-binding protein 1(4E-BP1).The results were used to explore the antidepressant mechanism of Jiaotai Pill.Results: 1.Effect of Jiaotai Pill and its separated recipes on body weight,sucrose preference,and open-field activity scoresChanges of body weight of rats: before the establishment of the model,there was no significant difference in the body weight of rats in each group.After modeling,the weight of rats in the model group was significantly lower than that in the blank group,with a significant difference(P < 0.01);compared with the model group,Jiaotai Pill,coptis,cinnamon each dose group and the positive drug group could antagonize the slow growth of rats’ weight,and the effect of high dose group of Jiaotai Pill and positive drug group was more obvious,with a significant difference(P < 0.01).The change of 1% sugar water preference rate in rats: before the establishment of the model,there was no significant difference in the 1% sugar water preference rate in each group.After the establishment of the model,the 1% sugar water preference rate of the model group was significantly lower than that of the blank group,with a significant difference(P < 0.01);compared with the model group,the 1% sugar water preference rate of the high dose group of Jiaotai Pill and the positive drug group was significantly higher,with a significant difference(P < 0.05).The changes of open field test experiment in rats: after 35 days of modeling,the number of erections and horizontal distance of rats in the model group were significantly reduced compared with those in the blank group,with a significant difference(P < 0.01);compared with the model group,the number of erections in each dose group of Jiaotai Pill,high dose group of coptis,high dose group of cinnamon and positive drug group was significantly increased,with a significant difference(P < 0.05 or P < 0.01),the horizontal distance of rats in each dose of Jiaotai Pill,high-dose cinnamon group and positive drug group increased significantly,with a significant difference(P < 0.05 or P < 0.01).2.The effect of Jiaotai Pill and its separated recipes on the level of PI3 K / Akt / m TOR signal pathway and the related indexes in the hippocampus of ratsThere were no significant differences in PI3 K,AKT,m TOR,and 4EBP1 protein expression among different groups(P > 0.05).Compared with the blank group,the expression level of p-PI3 K protein in the hippocampus of the CUMS model group was significantly reduced,with a significant difference(P < 0.05),compared with the model group,the high-dose group of Jiaotai Pill and the fluoxetine dose group were significantly increased the expression level of p-PI3 K protein,with a significant difference(P < 0.05);the expression level of p-AKT in the hippocampus of the CUMS model group was significantly reduced,with a significant difference(P < 0.01),compared with the model group,the high-dose group of Jiaotai Pill and the fluoxetine dose group were significantly increased the expression level p-AKT,with significant differences(P < 0.05);compared with the blank group,the expression level of p-m TOR protein in the hippocampus of the CUMS model group was significantly reduced,with a significant difference(P < 0.01),compared with the model group,the high-dose group of Jiaotai Pill and the fluoxetine dose group were significantly increased the expression level of p-PI3 K protein,with a significant difference(P < 0.05 or P <0.01);compared with the blank group,the expression level of p-4EBP1 protein in the hippocampus of the CUMS model group was significantly reduced,with a significant difference(P < 0.01);compared with the model group,the high-dose group of Jiaotai Pill and the fluoxetine dose group were significantly increased the expression level of p-4EBP1 protein,with a significant difference(P < 0.05);coptis dose groups,cinnamon dose groups Even Enough to varying degrees up p-PI3 K,p-AKT,p-m TOR,p-4EBP1 protein levels in the hippocampus,but not significantly.Coptis dose groups and cinnamon groups also increased protein expression levels,but there was no statistical significance.Conclusions:The antidepressant effect of coptis and cinnamon alone group was significantly lower than that of Jiaotai Pill group.The experimental results show that Jiaotai Pill produce a marked effect through the compatibility of coptis and cinnamon.The scientific connotation that Jiaotai Pill can make the heart and kidney communicate in an instant is developed through the common use of coptis and cinnamon.The mechanism of its action is preliminarily discussed,which may be related to the regulation of PI3 K / Akt / m TOR signal pathway by Jiaotai Pill in depression rats.