Effects of Danlong Xingnao Prescription on Learning and Memory Ability of Vascular Dementia Rats Based on PI3K/Akt/mTOR Signaling Pathway
Objective To explore the effects of Danlong Xingnao Prescription on the learning and memory ability of vascular dementia(VD)model rats based onPI3K/Akt/mTOR signaling pathway;To discuss its possible mechanism.Methods VD rat model was prepared using improved bilateral common carotid artery ligation method.Modeling rats were randomly divided into model group,nimodipine group and DanlongXingnao Prescription low-,medium-,high-dosage groups(3.7,7.4,14.8 g/kg),with 10 rats in each group.The sham-operation group only separated the arteries without ligation.Each medication group was given corresponding drugs by gavage,the sham-operation group and the model group were given equal amounts of physiological saline by gavage for 4 consecutive weeks.Morris water maze was used to test the learning and memory ability of rats,morphology of the hippocampus were observed by HE staining,immunohistochemistry was used to detect microvascular density and expression of vascular endothelial growth factor(VEGF),the activity of SOD,GSH-Px and the content of MDA in liver tissue were detected by biochemical method,RT-qPCR and Western blot were used to detect the mRNA and protein expression of PI3K,Akt,mTOR,hypoxia-inducible factor-1α(HIF-1α),VEGF,Bax and Bcl-2 in hippocampal tissue.Results Compared with the sham-operation group,the latency period of evasion was significantly prolonged,and the number of platform crossings was significantly reduced in the model group(P＜0.01),the cells in the hippocampal CA1 region had irregular morphology,loose arrangement,blurred boundaries,nucleolar condensation,and a large number of neuronal necrosis,the microvascular density and VEGF expression significantly increased(P＜0.01),the SOD and GSH-Px activity in hippocampal tissue decreased(P＜0.01),MDA content increased(P＜0.01),the expressions of HIF-1α,VEGF,Bax mRNA and protein in hippocampal CA1 region increased,and PI3K,Akt,mTOR,Bcl-2 mRNA and protein expression decreased(P＜0.01).Compared with the model group,the latency period of evasion were significantly shortened,and the number of platform crossings increased in the Danlong Xingnao Prescription groups(P＜0.05,P＜0.01),neuronal damage in hippocampal CA1 region was alleviated,microvascular density and VEGF expression increased(P＜0.05,P＜0.0 1),the activities of SOD and GSH-Px in hippocampal tissue increased(P＜0.05,P＜0.01),the content of MDA decreased(P＜0.05,P＜0.01),the mRNA and protein expressions of PI3K,Akt,mTOR,HIF-1α,VEGF,Bcl-2 in hippocampal CA1 region increased(P＜0.05,P＜0.01),the expression of Bax mRNA and protein decreased(P＜0.05,P＜0.01).Conclusion Danlong Xingnao Prescription can improve the learning and memory ability of VD model rats,promote angiogenesis,inhibit oxidative stress and apoptosis.The mechanism may be related to the up-regulation of PI3K/Akt/mTOR signaling pathway in hippocampal tissue.
万方数据
维普
