| Objective: To observe the effects of Mongolian medicine Zadi-5 on the signaling pathways of PI3K/AKT/BCI-2 in hippocampus of rats with chronic and mild unforeseeable depression,and to investigate the effects and mechanism of Zadi-5 on the apoptosis of hippocampal neurons in rats with depression.Adaptive methods: 100 male SD rats fed according to body weight were randomly divided into 10 groups after one week,10 in each group,normal control group,model group,Western medicine group,Zadi-5 high dose group,Zadi-5 medium dose group,Zadi-5 low dose group,LY294002 + Zadi-5 high dose group,LY294002 + Zadi-5 medium dose group,LY294002 + western medicine group and LY294002 group.Chronic mild unforeseeable stress(CUMS)combined with isolated feeding was used to establish the rat depression model.Fluoxetine was given daily by gastric gavage according to body weight,respectively,3.6mg/k·d,Zadi-5 0.4,0.8,1.6 mg/k·d.The model group and the normal group were given equal volume normal saline for 4 weeks.The behavioral changes of rats were observed by weighing the rats,sugar water consumption experiment,tail suspension experiment,open-field open-field experiment and Morris water maze experiment.Brain tissue was collected after the last administration,and the protein expression of PI3 K,Akt,bcl-2,Bax and caspase-3 in the hippocampal area of rats was detected by immunohistochemistry.The morphological changes of hippocampal nerve cells in each group were observed by HE staining,and the apoptosis of neurons in the hippocampal area of rats was detected by original terminal deoxynucleotide transferase labeling(Tunel)staining.Results:(1)Behavioral experiment: there was no significant difference in body weight,sugar water consumption,tail suspension experiment and open box experiment before modeling(P < 0.05).After modeling,compared with the blank group,the weight,sugar water consumption,open box test scores of rats in the model group decreased,while the tail suspension time and platform searching time increased(P < 0.05).Compared with the model group,the body weight,sugar water consumption and open box test scores of rats in the western medicine group,zaidi-5 high and middle dose groups increased significantly,while the tail suspension time and platform searching time decreased significantly(P < 0.05).(2)Physiological and biochemical experiments: compared with the blank group,the number of neurons in the hippocampus of the model group was significantly reduced,nuclear pyknosis,chromatin aggregation,apoptotic cells were significantly increased(P < 0.05),the content of PI3 K,Akt,bcl-2 protein in thehippocampus was significantly reduced(P < 0.05),the expression of Bax,caspase-3 was significantly increased(P < 0.05),the difference was statistically significant.Compared with the model group,the contents of PI3 K,Akt and Bcl-2 in the hippocampus of zaidi-5 high dose group,middle dose group and Western medicine group increased significantly(P < 0.05),the expression of Bax and Caspase-3 decreased significantly(P < 0.05),and the number of apoptotic cells in the hippocampus decreased significantly(P < 0.05).Conclusion: 1.Zadi-5 can inhibit the decreasing trend of body weight,sugar water consumption and open box experimental activity in depressed model rats,and reduce the time of tail suspension and platform seeking,which can significantly improve the depressive symptoms in depressed model rats.2.Zadi-5 can reduce the expression of Bax and Caspase-3 proteins in the hippocampus of rats,improve the contents of PI3 K,Akt and Bcl-2,and have a certain protective effect on hippocampal nerve cells.3.The protective mechanism of Zadi-5 against depression may be that it activates the PI3K/AKT/BCI-2 signaling pathway,thus regulating the balance of apoptosis. |
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