Studies On Mechanism Of XiaoYaoSan's Regulation On Feedback Of HPAA And GR,NMDAR In Chronic Stress Rat

Studies found that the acute stress has no distinctive impact to the construction of hippocampus.But under the station of chronic stress,the neurons of hippocampus would be atrophy even to death.The concrete mechanism is still unknown,but maybe the neural pathway of HPA- N-methyl -D-aspartic acid receptors(NMDAR) - GLucocorticoid receptor(GR)has played a significant role in the station.Under the physiological condi -tion,the pathway can exert a sere of biological effect on maintaining the excitable transmit between neurons and the excitability of neurons and brain.1,ObjectiveIf Chronic stress happen,HPA axis excitability would rise,excretion of Corticotrophin releasing hormone(CRH) would rise,corticosteroid level in blood would rise,body potential would be activated,then body can adapt the chronic stress.But if body under stress too long time,HPA axis 'function would keep exciting,high corticosteroid level would damnify brain hippocampus nerve cell badly,result in NMDAR of hippocampus nerve cell excess activation,GR especially iGR expression would reduce; HPA axis' s feedback would be weaken,all of this would aggravate high corticosteroid level in blood.So,the high corticosteroid level in blood is a important sign of chronic stress.This paper based on this theory, verify the chronic stress model by the DEXT.Then we treat the model by Xiaoyaosan and RU-38486,observing the expression of CRH mRNA,GR(iGR),NMDAR subfamily,studying the mechanism of Xiaoyaosan' s regulation chronic stress modle.2,MethodsWe studying the mechanism of Xiaoyaosan' s regulation on chronic stress model in the way that replicating the chronic stress model, verifying the chronic stress model through the DEXT,treating the model by Xiaoyaosan and RU-38486.1) detect the corticosteroid level in the serum of the rat with DEXT by Enzyme Linked Immunosorbnent Assay(ELISA);2) detect the expressions of Corticotrophin releasing hormone(CRH) mRNA in the brain paraffin sections of the chronic stress rat by insituhybridization;3) detect the expressions of intracellular GLucocorticoid receptor(iGR) in the brain paraffin sections of the chronic stress rat by fluorescence Immunohistochemsitry;4) detect the expressions of intracellular N-methyl-D-aspartic acid receptors subspecies(NR1,NR2A,NR2B) in the brain paraffin sections of the chronic stress rat by fluorescence Immunohistochemsitry.3,Result1) In our research,the disorder of the HPAA' s function in the chronic stress rat include that the high corticosteroidlevel in blood,the high expressions of Corticotrophin releasing hormone(CRH) mRNA in hypothalamus paraventricular nucleus,the low expressions intracellular GLucocorticoid receptor(iGR) in brain hippocampus, the high expressions of intracellular N-methyl-D-aspartic acid receptors subspecies(NR1,NR2A,NR2B) in brain hippocampus;2) The level of corticosteroid in blood in group of the chronic stress rat doesn't decilne in DEXT,by contraries,the level of corticosteroid in blood of the chronic stress rat in DEXT of Xiaoyaosan group and RU-38486 group decline obviously:3) The expression of the Corticotrophin releasing hormone(CRH) mRNA at hypothalamus paraventricular nucleus of the rat in single chronic stress group raise obviously;the expression of the Corticotrophin releasing hormone(CRH) mRNA at hypothalamus paraventricular nucleus of the rat in Xiaoyaosan group and RU-38486 group doesn't ascend;4) The expression of intracellular GLucocorticoid receptor(iGR) at brain hippocampus of the rat in single chronic stress group decline obviously;the expression of intracellular GLucocorticoid receptor(iGR) at brain hippocampus of the rat in Xiaoyaosan group and RU-38486 group doesn't decline;5) The expression of intracellular N-methyl-D-aspartic acid receptors subspecies(NR1,NR2A,NR2B) in brain hippocampus of the rat in single chronic stress group raise obviously;The expression of intracellular N-methyl-D-aspartic acid receptors subspecies(NR1,NR2A,NR2B) in brain hippocampus of the rat in Xiaoyaosan group and RU-38486 group doesn't ascend.4,ConclusionBased on our research,we can make the flowing conclusion:chronic stress modle in our research is successful,Xiaoyaosan can depress the expressions of intracellular N-methyl-D-aspartic acid receptors subspecies(NR1,NR2A,NR2B) in brain hippocampus of the chronic stress rat,raise the expressions of intracellular GLucocorticoid receptor(iGR) in brain hippocampus,depress the level of corticosteroid in blood, depress the expression of the Corticotrophin releasing hormone(CRH) mRNA in hypothalamus paraventricular nucleus,partly resume the function of the HPAA on feedback of the chronic stress rat.Xiaoyaosan can effectively depress the excitability of HPA axis caused by the chronic stress,regulate function of HPA axis through which above to protect the neurons from damage,resume the feedback function of the HPA axis partly.