Objective It is to investigate the neuroprotective effect of Dihuang Decoction on vascular dementia(VD)model rats based on phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt)signaling pathway mediated by vascular endothelial growth factor(VEGF).Methods Sixty SD male rats were taken,in which 10 rats were randomly selected as sham operation group,and the remaining rats were used to establish VD models by 2-VO method.The modeling rats were screened by the method of Zea-Longa 5-grade 4-point scoring for neurological deficits.45 successfully modeled rats were randomly divided into 5 groups,with 9 rats in each group.The high,medium and low dose groups of Rehmannia Decoction were respectively given Rehmannia Decoction 3 g/kg,1.5 g/kg and 0.75 g/kg by gavage,the nimodipine group was given nimodipine suspension 6.25 mg/kg by gavage,and the sham operation group and model group were given equal volumes of saline by gavage,all once daily.After 30 days of consecutive gavage,the neural function of the rats was assessed by Zea-Longa scores,the learning and memory abilities of the rats were detected by Morris water maze,the morphology and struc-ture of neurons in cortical areas were observed by HE staining,and the protein expressions of phosphorylated phosphatidyli-nositol 3-kinase(p-PI3K),phosphorylated protein kinase B(p-Akt),B-lymphoblastoma-2 gene(Bcl-2),Bcl-2-related X protein(Bax),VEGF receptor 2(VEGFR2)were detected by Western blot.Results Compared with the sham operation group,the Zea-Longa scores of rats in the model group were significantly increased(P<0.05),the escape latency from the 3rd day to 5 th day were all significantly prolonged(all P<0.05),the times of crossing the effective area were signifi-cantly reduced(P<0.05),the morphology and structure of neurons in cortical areas were impaired,and the relative ex-pressions of p-PI3K,p-Akt,and Bcl-2 proteins in the brain tissues were significantly reduced(all P<0.05),and the rel-ative expression of Bax protein was significantly increased(P<0.05).Compared with the model group,the Zea-Longa scores of rats in each treatment group were significantly decreased(all P<0.05),the escape latency from the 3rd day to 5 th day were all significantly shortened(all P<0.05),the times of crossing the effective area were significantly increased(P<0.05),the injury of morphology and structure of neurons in cortical areas were improved,and the relative expressions of p-PI3K,p-Akt,and Bcl-2 proteins in the brain tissues of the medium and low dose groups of Rehmannia Decoction,the relative expressions of p-PI3K,p-Akt proteins in the brain tissues of nimodiping group,and the relative expression of VEG-FR2 protein of the medium dose group of Rehmannia Decoction were all significantly increased(all P<0.05),and the rel-ative expressions of Bax protein of nimodiping group,medium and low dose groups of Rehmannia Decoction were signifi-cantly decreased(P<0.05),there was no significant difference in these indexes among every treatment group(all P>0.05).Conclusion Rehmannia Decoction can alleviate neuronal injury,promote angiogenesis and inhibit apoptosis in the cortical area of VD rats,thus to improve their neurological function and learning and memory abilities,the mechanism may be related to VEGF-mediated PI3K/Akt signaling pathway.
vascular dementiaRehmannia Decoctionangiogenesisphosphatidylinositol-3-kinaseprotein kinase B
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