Effect Of Dendrobium Nobile Lindl Alkaloids On Anxiety Rats Model Induced By Chronic Stress

Objective:To investigate the effect of Dendrobium nobile Lindl alkaloids（DNLA）on anxiety rats model induced by chronic stress,and explore the possible mechanisms.Methods:Twenty-four male SD rats were randomly divided into three groups:control group（C）,anxiety model group（M）and model+DNLA group（M+DNLA）,and each group contained 8 rats.For M group,rats were induced by chronic stress.M+DNLA group rats were orally given DNLA（20 mg/kg/day）.C group and M group rats were given an equivalent volume of 1%Tween 80.Rats were treated daily for 28days.The behavior of all rats was evaluated by elevated plus-maze test（EPM）and open field test（OFT）.The neuronal damage in the hippocampus CA2 region and the cortex were observed by Nissl staining.High performance liquid chromatography with electrochemical detector technology was used to detect the level of 5-hydroxytryptamine（5-HT）and its metabolite 5-hydroxyindoleacetic acid（5-HIAA）from the prefrontal cortex dialysate,cortex tissue and serum.The activities of tryptophan hydroxylase（TPH）and monoamine oxidase（MAO）,the contents of corticosterone（CORT）and adrenocorticotropic hormone（ACTH）in cortex tissue were detected by enzyme-linked immunosorbent assay.Immunohistochemistry was used to detect the expressions of 5-HT system-associated protein including synaptic vesicular monoamine transporter 18A1（SLC18A1）,synaptosomal-associated protein25（SNAP25）,5-HT_1A receptor(5-HT_1AR)and 5-HT transporter（SERT）;γ-aminobutyric acid A receptor（GABA_AR）,N-Methyl-D-Aspartate receptor（NMDAR）;HPA axis-associated protein including corticotrophin releasing factor 1 receptor（CRF1）and glucocorticoid receptor（GR）.Results:As compared with control group,in model group,the distance and the number entering into open arms were significantly decreased in EPM.The distance in central zone and the total distance were significantly decreased in OFT.A decrease of neurons number in cortex and the hippocampal CA2 region were observed.5-HT and5-HIAA levels from prefrontal cortex dialysate,cortex tissue and serum were significantly increased.The activities of TPH and MAO,and the levels of CORT and ACTH were significantly increased.The expressions of SLC18A1,SNAP25,5-HT_1AR,GABA_AR and GR were significantly decreased,and the expressions of SERT,NMDAR1 and CRF1 were significantly increased.However,DNLA treatment significantly increased the distance and the number entering into the open arms in EPM.The distance in central zone and the total distance were also significantly increased in OFT.DNLA increased the number of neurons in the cortex and the hippocampal CA2 region.DNLA decreased the levels of 5-HT and 5-HIAA from dialysate,cortex and serum.Moreover,DNLA decreased the activities of TPH,MAO,and the levels of CORT,ACTH.DNLA significantly increased the expressions of SLC18A1,SNAP25,5-HT_1AR,GABA_AR and GR.DNLA significantly decreased the expressions of SERT,NMDAR1 and CRF1.Conclusion:DNLA can attenuate anxiety symptoms of rats induced by chronic stress.The mechanisms may be related to attenuate 5-HT system,regulate GABA_AR,MMDAR and HPA axis.