Effects Of Lishu Shugan Anshen Decoction On The Nerve Damage Of The Prefrontal Cortex-edge (hippocampus, Amygdala) In Rats With Anxiety Depression

Objective To Establish an animal model of anxious depression,from the four aspects of behavior,blood biochemistry,histomorphology and molecular biology,to investigate the effect of Baihe Shugan Anshen on prefrontal-Margin(hippocampus and amygdala)of important target area in rats with anxious depression by the neuro-endocrine-immune dysfunction as the starting point.To explore the mechanism of its anti-anxiety and depression of the mechanism for the prevention and treatment of the disease to provide new ideas and methods.Methods SD rats were randomly divided into 7 groups according to body weight: anxious depression model group,Positive drug(venlafaxine 6.75 mg/kg)group,compound Baihe Shugan Anshen,-high,-middle,-low(24.28 g/kg,12.24 g/kg,6.12 g/kg)group,and control group and vehicle group.Chronic restraint stress and caged rearing,and subcutaneous injection of CORT(30 mg/kg)for 21 consecutive days to build anxious depression model.At the same time,the models was administered by intragastric administration.Subcutaneous injection of physiological saline +5%DMSO for vehicle group.The control group was fed normally.The changes in body weight were measured weekly,the behavioral changes of the rats were observed by the Conditional Fear test,elevated maze test,open-field test and forced swimming test.Corticosterone(CORT),adrenocorticotropic hormone(ACTH)and adrenocorticotropic hormone(CRH)were measured by ELISA.Morphological changes of hypothalamus,pituitary,adrenal gland Prefrontal cortex,hippocampus(CA3,DG),amygdala were observed by HE staining.The levels of 5-HT,NE and DA in the prefrontal-marginal(hippocampus and amygdala)tissues were detected by HPLC-ECD.Elisa assay was used to detect the expression of TNF-a in plasma and prefrontal-marginal(hippocampus and amygdala)The expression of IDO,GR,BDNF and NPY in prefrontal-marginal(hippocampus and amygdala)tissues were detected by western-blotting.Results(1)Weight change and behavior: Compared with the control group,weight changes gradually increased,the number of open arms,the percentage of open arms time and the amount of self-inquiry activity of the anxious depression model group were significantly decreased(P <0.05 or P <0.01),and the immobility time of Freezing and swimming significantly increased(P <0.05 or P <0.01).Compared with the anxious depression model,The above indexes in the high-dose group and the positive drug group were significantly reversed.(2)HPA axis structure function: Compared with the control group,the structure of the hypothalamus,pituitary and adrenal gland in anxious depression showed obvious pathological changes.The plasma levels of CORT,ACTH and CRH were increased(P <0.01).Compared with the model group of anxious depression,the high dose of Baihe Shugan Anshen can significantly protect the structural changes of HPA axis and ease its function hyperthyroidism;(3)prefrontal-marginal(hippocampus and amygdala)system structure and protein content: Compared with the control group,the structure of the prefrontal cortex,hippocampus and amygdala in anxious depression model group had obvious pathological changes,and the neuronal cells were atrophy or decreased.The contents of GR,BDNF and NPY were significantly decreased(P <0.01);Compared with the model group,Baihe Shugan Anshen can significantly protect the prefrontal-marginal(hippocampus and amygdala)structural nerve regeneration,adjust the expression of the expression of GR,BDNF and NPY(P <0.05 or P <0.01).(4)cytokines and monoamine neurotransmitter: Compared with the control group,the plasma TNF-a content in the model group was significantly higher(P <0.01),and the expression of TNF-a and IDO in the prefrontal cortex,hippocampus and amygdala were significantly up-regulated(P < 0.05 or P <0.01).The levels of 5-HT,DA and NE in monoamine neurotransmitters were down-regulated(P <0.05 or P <0.01).Compared with model group,Baihe Shugan Anshen can significantly reverse the above changes in the indicators(P <0.05 or P <0.01).Conclusion(1)Baihe Shugan Anshen can significantly improve the body weight change and anxiety and depression behavior of anxious depression rats.(2)Baihe Shugan Anshen can significantly improve the structural disorder of endocrine HPA axis in rats with anxiety and depression.(3)GR / BDNF / NPY signal transduction may be one of the key molecular mechanisms of the regulation of the neural regeneration of the prefrontal-marginal(hippocampus,amygdala)system in the rats with anxious depression.(4)Baihe Shugan Anshen can reduce the changes of TNF-a-IDO-5-HT signaling pathway and other monoamine neurotransmitters DA and NE,and reduce the prefrontal-marginal(hippocampus,amygdala)System neurotoxicity.