Effects Of Mongolian Medicine Gaoyou-13 Flavor Pills On Neuropeptides In Chronic Stress Depression Model Rats

Objective:In this study,a rat model of chronic stress depression was prepared by random unforeseen stress combined with solitary raising,and the mechanism of antidepressant effect of Gaoyou-13 was investigated by observing the changes in rat behavior,neuropeptides and inflammatory cytokines.Methods: 1.Grouping method: 32 SD male rats of clean grade were reared adaptively for one week in a breeding room with suitable temperature and humidity,and then randomly divided into blank control group,model group,Gaoyou-13 group and fluoxetine group(positive control group),with 8 rats in each group.Four rats in the blank control group were housed in one cage,and the rats in the other groups were housed in single cages.2.Preparation of the model: one stimulus is randomly given every day,and the same stimulus cannot be used continuously for the same rat.The type of suimulus mainly includes wet bedding(24 h),fasting(24 h),water deprivation(24 h),clipping Tail(1 min),reverse day and night(12 h),swimming in ice water(4 ℃ water,5 min),restraint(2 h).The rat model of chronic stress depression was established by random unforeseen stress combined with solitary raising.3.Administration method: the blank control group and the model group were administered with distilled water 1 hour before the modeling stimulation.Fluoxetine group was administered with 3.3 mg·kg-1 fluoxetine solution 1 hour before the modeling stimulation.Rats in the Gaoyou-13 group were administered Gaoyou-13 solution at 0.5g·kg-1 level 1 hour before the modeling stimulation.The administered level were all at 10 m L·kg-1 for 42 consecutive days.4.Detection indicators: Behavioral experiments include open field experiments,sugar water experiments and body weight experiments.Enzyme-linked immunosorbent assay(ELISA)was used to measure the contents of NPY,CCK and SP in peripheral serum,pituitary gland and colon tissues of rats,and the contents of serum IL-6 and IL-8.Results:1.Behavioral test results: the weight gain of rats in the model group was slower than that of the blank control group.There were significant differences between the two groups on day 14,day 28,and day 42(P <0.05 or P <0.01).Compared with the model group,the weight of the rats in different intervention groups increased significantly(P <0.05 or P <0.01).In the open field experiment,the number of parallel cross-grid movement and upright movement of the rats in the model group was significantly reduced compared with the blank control group.The difference was significant(P <0.01)).Parallel cross-grid movement and upright movement of rats were significantly improved after different intervention(P <0.05 or P <0.01).In the sugar water experiment,compared with the blank control group,the sugar water preference of the rats in the model group decreased,and the difference was significant(P <0.01).The sugar water preference of the rats in different intervention groups was significantly higher than that of the model group.Especially Gaoyou-13 group showed dramatic improvement and the difference is significant(P <0.05 or P <0.01).2.Tested results of NPY,CCK,and SP level in serum,pituitary,and colon tissues: In terms of NPY content detection,the NPY contents in the serum,pituitary,and colon tissues of the model group were significantly lower than those in the blank control group,and the difference was significant(P <0.05 or P < 0.01).After fluoxetine and Gaoyou-13 intervention,the NPY content in serum,pituitary and colon tissues of rats was significantly increased,and the difference was significant(P <0.05 or P < 0.01).In terms of CCK content detection,the CCK content in the serum,pituitary,and colon tissues of the rats in the model group was significantly increased,and the difference was significant(P <0.05 or P <0.01).After applying fluoxetine and Gaoyou-13,the CCK content in rat serum,pituitary,and colon tissue was significantly decreased and the difference was significant(P <0.05 or P <0.01).In terms of SP content detection,the SP content in the serum,pituitary,and colon tissue of rats in the model group was significantly increased,and the difference was significant(P <0.05 or P <0.01).After the implementation of fluoxetine and Gaoyou-13,the SP content in the serum,pituitary,and colon tissue of rats was significantly reduced and the difference was significant(P <0.05 or P <0.01).3.Serum IL-6 and IL-8 test results: the serum IL-6 and IL-8 levels of rats in the model group were significantly increased and the difference was significant(P <0.01).After using fluoxetine and Gaoyou-13,the level of serum IL-6 and IL-8 in model rats was effectively reduced compared to the model group and the difference is significant(P <0.05 or P <0.01).Conclusions:After chronic stress stimulation,rats showed behavioral behavioral manifestations such as decreased appetite,anhedonia,and fear of new environment.The results show that the depression model is successfully prepared in this experiment.After the intervention of Goyou-13,it can effectively improve the depression-like behavioral changes of CUMS rats,regulate the contents of NPY,CCK,SP and IL-6 and IL-8 in serum,pituitary and colon tissues of CUMS rats.It is suggested that the regulation of immunity and brain-gut axis function in CUMS rats is one of the anti-depressive mechanisms of Goyou-13.