Study On Changes And Mechanisms Of Molecular Immunology Of Hypothalamic Pituitary Adrenal Thymic Axis In The Kidney-Yang Deficiency Model Induced By Overfatigue And Sexual Overstrain

Objective:This study explored the mechanism of celluar and immunological regulation in the Kidney-Yang deficiency syndrome mice model induced by overfatigue and sexual overstrain. Meanwhile, the effects of this model on hypothalamic pituitary adrenal thymic axis were further examined.Methods:In this study, a mice model of Kidney-yang deficiency syndrome was used as experimental animal which had been established by us before. The mice were categorized into three groups at random:normal control group; Kidney-Yang deficiency model group and JIGUISHENQI bolus therapy group. The morphological changes of mice thymus tissue were observed after HE staining. Ultramicrostructure were observed with transmission electron microscopy as well. Changes of lymphocyte transformation test and Thl/Th2 cytokines, including IFN-?, IL-2 and IL-4 were examined in different groups. The mRNA levels of cytokines including IFN-y and IL-4 were assessed by RT-PCR. Furthermore, the cell cycle and apoptosis rate in mice lymphocytes were detected by using FACS. Then the contents of plasma adrenal axis hormones were measured with radioimmunoassay method. In addition, immune-related genes from the cerebral gene expression profiles were screened by means of thegene microarry technology.Results:The morphological and ultramicrostructural changes of thymus tissue, the reduction of lymphocyte transformation rate in mice splenocytes, significant decrease of Thl cytokine including IFN-y and IL-2 and of plasma adrenal axis hormone level, and the marked increase of Th2 cytokine including IL-4 and of apoptosis rate were observed in the Kidney-Yang deficiency syndrome mice model caused by overfatigue and sexual overstrain. Meanwhile,36 out of 485 significant immune-related genes from the cerebral gene expression profiles were screened and further analyzed. It can be found that JIGUISHENQI bolus could exert immuno-regulatory impacts on the above-mentioned disturbances.Conclusion:The Kidney-Yang deficiency syndrome mice model caused by overfatigue and sexual overstrain presented the tectological and ultramicrostructuraldegradation of thymic tissue, imbalance between Thl and Th2 cytokines, and blocking passways of cell cycle, leading to the immune dysfunction, which may be due to changes of immune-related genes. JIGUISHENQI bolus could regulate immune function by adjusting cytokine levels, enhancing adrenal axis hormone contents, and reducing apoptosis. In the meanwhile, it is further tested on the level from the organs to cells to genes that the Kidney-Yang deficiency syndrome is related to the dysfunction of hypothalamic pituitary adrenal thymic axis.