Effects On HPTA And Testis Gene Profile Affected By Kidney-yang Deficiency Induced By Overfatigue And Sexual Overstrain And Therapy Of Invigorating The Kidney-yang

Objective:This experimental study focused on variations of neuroendocrine, pathological morphology, apoptosis-related proteins of hypothalamic-pituitary-thyroid-axis and changes of testis gene profile of hypothalamic-pituitary-gonad-axis in kidney-yang deficiency syndrome mice model induced by overfatigue and sexual overstrain. Mealwhile, the effects of Jinguishenqi bolus on thyroid-axis and gonad-axis were explored in kidney-yang deficiency syndrome mice model.Methods:The mice model of kidney-yang deficiency syndrome induced by overfatigue and sexual overstrain were established. Observe the morphological changes and ultrastructural variation of thyroid with light microscope and electron microscopy, detect the content of thyroid axis hormone in serum such as TSH, T3 and T4 by radioimmunoassay, determine the expression of Fas, FasL, Bcl-2, Bax and Caspase-3 in mice thyroid by immunohistochemical method among control group, kidney-yang deficiency syndrome group and treatment group. In addition, two scatter plots of gene expression profile were drawn and differentially expressed genes were detected and screened.Results:1. Mice model of kidney-yang deficiency syndrome induced by overfatigue and sexual overstrain were established successfully by observing the changes of mice temperature, weight and general condition.2. Pathmorphological injuries of thyroid glands were observed in mice with kidney-yang deficiency. Jinguishenqi bolus had certain modulation of morphological and ultrastructural variation. 3. There had been a decrease of hormone level of thyroid axis in serum in mice model of kidney-yang deficiency syndrome, but with kidney-yang nourishing therapy the serum hormone level increased.4. Expression of apoptosis related gene Bax in mice model group were higher than that in mice control group, but expression of Bax and FasL in treatment group mice lower than those in mice model group.5. Two scatter plots of gene expression profile were drawn with model/control group and treatment/model group. Differentially expressed genes were screened, including 2425 up-regulated genes and 3080 down-regulated genes in model/control group,99 up-regulated genes and 96 down-regulated genes in treatment/model group. There were ten genes among up-regulated genes in model/control group but down-regulated in treatment/model group, and fifteen genes among down-regulated genes in model/control group but up-regulated in treatment/model group. These genes were mainly related to cellular structure/function, material/energy metabolism, signal transduction/relay, transcription/translation, proliferation/differentiation, cell cycle and cell apoptosis. Abnormal expression of testis genes such as Usp39, Jam2, Cdc20, Arg1 and Akap10 in model/control group was modulated in treatment/model group by Jinguishenqi bolus.Conclusion:The results indicate that overfatigue and sexual overstrain could lower the hormone level of thyroid axis, promote cell apoptosis of thyroid by high expression of apoptosis related gene Bax and change the level of testis genes expression related to cell cycle, energy metabolism and spermatogenesis. Jinguishenqi bolus could inhibit cell apoptosis by decreasing the level of Bax and FasL to promote thyroid axis function and modulate the level of testis genes expression related to cell cycle and spermatogenesis to promote gonad axis function.