Establishment And Application Of 5-HT_1AR Cell Membrane Chromatography Model

5-hydroxytrptamine(5-HT) also known as serotonin, regulating functional activities of many physiological and pathological states in brain, 5-HT reduced and 5-HT receptor became less sensitive were main reasons of depression. 5-HT1 A receptor(5-HT1AR) is accounted for the largest proportion of 5-HT receptors, closely related to depression, its agonists are used for treatment of depression. 5-HT1 AR expressed in T and B lymphocytes, positivity of 5-HT1 AR protein was detected in86.25 %. Depression is a mood disorder, has high incidence rate, high suicide, and low treatment rate. But so far, the pathogenesis of depression is not very clear. Therefore, 5-HT1 AR is an important target spot, which plays an important role in antidepressant screening.Cell membrane chromatography(CMC), was that cell membrane were collected and incubated with silica to be absorbed to form a cell membrane stationary phase(CMSP), then the CMSP was packed into acolumn to build up a CMC model. At present, CMC has been used to screen active compounds from traditional Chinese medicine. Agonists exert their therapeutic effect, the combination between drug molecules and receptor is premise. CMC is an effective method for separating active component acting on a specific receptor, these active compounds whether are lead compounds could be verificated by pharmacology.In this thesis, 5-HT1 AR CMC model was esteblished by T lymphocytes. First, 5-HT1 AR agonists(5-HT, Buspirone, and 8-OH-DPAT)were used to validate its effectiveness. Second, three wolfberry extract which containing three agonists respectively were used to investigate its drug screening ability. Last, the model was used to screen new drugs.The first part, overviewed the research progress of depression(including definition, classification, pathogenesis, and5-HT1 AR agonists, etc.) and CMC(including definition, characteristics,application). In the second part, introduced the establishment of 5-HT1 AR CMC model(preparation of cell culture, extraction and separation of cell membrane, establishment of CMSP, package of column), three agonists(5-HT, Buspirone, and 8-OH-DPAT) were used to demonstrate whether 5-HT1 AR CMC model was established successfully. In the third part, the screening ability of 5-HT1 AR CMC model was researched. In the fourth part, introduced the application of 5-HT1 AR CMC model. The fifth part was the conclusion and prospection. 5-HT1 AR CMC model wasestablished successfully, its screening capacity was very prominent,through this method, a compound was screened, retention time was similar to the existing agonists, results were satisfactory. 5-HT1 AR CMC is a simple and effective method, which could be used to screen active compounds acting on 5-HT1 AR, its screening ability is very prominent,could be used to screen compounds particularly which acting on 5-HT1 AR,it has an important reference meaning for the potential depression agonists discovery and research.