The Effects And Mechanism Of The Novel Modified Kai-xin-San On Gastrointestinal Comorbidity Of Depression In CUMS Rats Model

Objective:As the global economic development and gradually fierce social competitiveness,the incidence of depression is increasing.Depression brought a huge burden to the society and family,and it has become a worldwide public health problem.Gastrointestinal dysfunction as one of the body disease of depression,is a kind of comorbidities with depression,and depression brings significant impact to the patient's quality of life.KXS(Kai-Xin-San)is a kind of ancient prescription to treat mental illness,and is effective for treating depression.However,the curative effects and mechanism of KXS in treating gastrointestinal comorbid depression are seldom reported.According to the mechanism of depression and gastrointestinal comorbidity,we add Ligusticum Chuanxiong Hort and Valeriana officinalis L to KXS original recipe and make up the novel modified Kai-Xin-San,called KXS(+),in order to improve its'antidepressant effect and the gastrointestinal function.Methods:This experiment used the clean level of 2 months aged 84 male SD rats,and the rats were divided into the Control,chronic unpredictable mild stress(CUMS),Fluoxetine,KXS,KXS(+)Low dose,KXS(+)Medium dose,KXS(+)High dose group,in which 12 rats in each group.In addition to the Control,the other groups were received CUMS stimulation methods for 28 days,and the medicine were given at the first day of stimulation.We observed and recorded the general status,body weight,changes in the rate of sugar water preference of rats in the process.Then we detect the open field experiment,forced swimming test,gastric residual rate and the intestinal propulsion in the CUMS model.We used Western Blot method to detect the changes of protein in the hippocampus,prefrontal cortex,stomach,and colon of rat models,and we used HE staining to observe the pathological changes of gastrointestinal morphology in rats.Results:We successfully mimicked the CUMS rats model,and found that the CUMS rats model were with obviously depressive behavior and increasing gluta-mate receptors expression in hippocampus.At the same time,CUMS rats model had abnormal gastrointestinal dynamics and pathological changes,suggesting that CUMS rats models were in gastrointestinal comorbidity status during depression.The novel modified Kai-Xin-San can significantly improve the rats' general status,body weight,depression behavior performance,and the novel modified Kai-Xin-San can improve the gastrointestinal dynamics and pathology manifestations in the CUMS rats model.Besides,the novel modified Kai-Xin-San can reduce the expression of glutamate receptors in hippocampus and gastrointestinal tract in CUMS rats model.Conclusion:Our results showed that KXS and the novel modified Kai-Xin-San were effective in treating CUMS rats model,and could improve the symptoms of the gastrointestinal dysfunction in depression.Related mechanism studies have shown that,the novel modified Kai-Xin-San was neuroprotective via inhibiting the glutamate excitotoxicity in hippocampus and gastrointestinal tissue,and then it improved the gastrointestinal comorbidity status in CUMS rats model.In addition,the effects of the novel modified Kai-Xin-San were superior to the KXS.