Effects Of Salidroside On Behavior And Its Underlying Mechanisms In PTSD Rats

Posttraumatic stress disorder(PTSD)leading to depression,schizophrenia,suicide etc,is a kind of mental disease caused by the changing structure and function of the nervous system,and patients experienced many major traumatic events,such as traffic accident,earthquake,war and so on,which may seriously affect the life quality of patients,and bring heavy economic burden to the family and society.At present,the main treatment methods of PTSD are western medicine treatment,traditional Chinese medicine treatment and psychological intervention,among which traditional Chinese medicine,because of its advantages of less side effect,abundant resources,low price and so on,has been paid more and more attention,and although the mechanism is not clear.It has been found that traditional Chinese medicine can significantly improve the symptoms of PTSD,providing a theoretical basis for continuing to find traditional Chinese medicine for treatment of PTSD.Rhodiola is one of the plants originals and the traditional Tibetan medicine which is commonly used in clinical medicine,and what’s more,salidroside is a kind of phenethyl alcohol extract from Rhodiola root.With the gradual deepening of salidroside research,it has been found that there is a wide range of effects of salidroside,such as anti hypoxia,promoting nerve repair,anti oxidation,enhance immunity and anti-tumor,and recently it also has found that salidroside can effectively improve cognitive function and the level of learning and memory.Therefore,it is concluded that salidroside may be used to treat PTSD,providing new ideas for the future development of PTSD drugs and the study of its mechanism.In order to investigate the effects of salidroside on behavior and its underlying mechanisms in PTSD rats,rats first are stimulated by using single-prolonged stress(SPS)to prepare PTSD model,then,salidroside treatment is performed by intraperitoneal administration,and the therapeutic effect is evaluated through the behavior identification.Finally,the effects of salidroside on apoptosis,synaptic changes and antioxidation of hippocampal neurons are investigated by histological and molecular examination,and its underlying mechanisms are further explored.The study is sure to provide a theoretical basis for the development and application of salidroside as an adjunctive therapy in PTSD.Main research contents:1.Preparation of PTSD animal model and drug treatmentPTSD animal model was prepared by SPS method.Female SD rats(230±25 g)were randomly divided into control group,PTSD group,salidroside low dose group(25 mg/kg),middle dose group(50 mg/kg)and high dose group(75 mg/kg),and there are 10 rats in each group.The salidroside intervention groups were given intraperitoneal injection of different doses of salidroside,and the control group and PTSD group were injected with the same amount of physiological saline.The effects of the drug were preliminarily evaluated through the changes of body weight and mental state.2.The effects of salidroside on the behavior of PTSD ratsThe effects of salidroside on behavioral improvement of PTSD rats were further evaluated by the results of refusing to capture test,open field,elevated plus maze and Water Maze experiments,comparing the behavioral differences between groups.3.The mechanisms of salidroside on behavioral improvement in PTSD ratsThe neurons number,morphology,neuronal apoptosis,and the distribution and density of dendritic spines in hippocampus CA1,CA3 and DG were investigated by using HE,Nissl,Golgi-Cox and TUNEL histological staining,and the protective effects of salidroside on hippocampal neurons,synaptic changes of hippocampal neurons were observed in PTSD rats,and its underlying histological and pathological mechanisms were further explored.The levels of oxidative stress molecular malondialdehyde(MDA)and superoxide dismutase(SOD)in serum,the expression of hippocampus neurons apoptosis related protein Bcl-2 and Caspase-3,and synaptic plasticity related proteins Synapsin I and p-CREB were respectively measured by antioxidant test,immunofluorescence staining and Western blot,and the molecular mechanisms of the effects of salidroside on behavioral improvement in PTSD rats were further explored.Results and conclusions:1.The animal model of PTSD was successfully established,and based on the changes of body weight and the mental state of PTSD rats before and after administration of salidroside,it could be preliminary concluded that salidroside to some extent could improve behavior of PTSD rats.2.In a certain extent,it is showed that salidroside can increase the exploratory behavior,reduce the anxiety,and improve the levels of learning and memory by using refusing to capture test,open field,elevated plus maze and Water Maze experiments.The exploratory behavior,anxiety,learning and memory ability of PTSD rats are all improved when intervened by salidroside.3.The results of HE,Nissl,Golgi-Cox and TUNEL staining showed that the histological and pathological mechanisms of salidroside on improving the behavior of PTSD rats may be performed by inhibiting the apoptosis of hippocampal neurons and protecting the morphology and number of dendritic spines.4.The results of antioxidant test,immunofluorescence staining and Western blot indicated that the molecular mechanism of the improving effects of salidroside on behavior of PTSD rats may be achieved by inhibiting the apoptosis of hippocampal neurons and the regulation of synaptic plasticity through the antioxidant activity of salidroside.