| Objective:Angiogenesis is the key factor for the ischemic neuron survival after cerebral ischemic injury and is closely correlated with the level of cognitive impairment. This study explored the effect of Shouwuyizhi Capsule on angiogenesis in rats with vascular cognitive impairment through the regulation of the VEGF-Notch/Delta cascade signaling pathway from molecular and cellular level, and therefore provides the preliminary experimental data and theoretical base for the treatment of tonifying the kidney and activating the blood for vascular cognitive impairment.Method:SD rats were used and the VCI model was established with MCAO.100 rats were chosen from 120 rats by Morris water maze and randomly divided into sham operation group, model group, Naofukang group and Shouwuyizhi group. After 4 weeks'medication, the rats'behavioral change was detected by Morris water maze and the cerebral histomorphological change was observed by HE stain and transmission light microscope.Ⅷfactor expression was measured by immunohistochemistry method and the expression of the genes of Notch4, Delta4, VEGF, VEGFR-2 was measured using real time PCR.Results:The escape escape latency of rats of model group was significantly longer than that of rats of shan group (P<0.01); The escape escape latency of rats of Naofukang group and Shouwuyizhi group were shortened successively.Compared with sham group,Shouwuyizhi group had no significant difference (P>0.05), while Naofukang group had the significant difference (P<0.01); Compared with Naofukang group, Shouwuyizhi group had the significant difference (P<0.01)。About the microvessel dencity of ischemia cerebral tissue,all of the other three groups were higher than sham group with the significant difference(P<0.01); Compared with model group,Naofukang group and Shouwuyizhi group had the significant difference (P<0.01); Shouwuyizhi group had no difference with Naofukang group (P>0.05)。The content of cerebral tissue of angiogenesis factors (VEGF,VEGFR-2, Notch4,D114) of rats model with vascular congnitive impairment were higher than the rats of sham group (P<0.01); After the treatment,the content of theses factors were further highter than model group.Except VEGFR-2,the content of VEGF,Notch4,D114 of Shouwuyizhi group were highter than Naofukang group (P<0.01, P<0.05).In Shouwuyizhi group,the contents of VEGF and that of D114 had significantly correlation (P<0.01).The content of serum anti-inflammatory cytokines ((IL-4, IL-10) of rats model with chronic inflammatory disease were lower than these of normal rats; the differences were very significant (P<0.01). After treatment, pro-inflammatory cytokine levels of the treatment group had decreased anti-inflammatory cytokine levels were elevated. At the regulation of IL-4, IL-8, IL-10, IL-1(3 the therapeutic effects of Jingangteng capsule group were better than GuizhiFuling capsule group and Shaofuzhuyu group, At the regulation of TNF-a, therapeutic effects of Guizhi Fuling Capsule medium dose group and Shaofuzhuyu group were better than Jingangteng capsule group.The expression of adhesions related immune molecules(TNF-α, TGF-β1, VEGF, ICAM-1, MMP-2) in model rats uterine tissue elevated above normal group, the differences were very significant (P<0.01) After treatment, expression of TNF-αTGF-β1 ICAM-1 in the treatment group had decreased, and MMP-2 had elevated. therapeutic effects of Guizhi Fuling Capsule medium dose group and Shaofuzhuyu group were better than Jingangteng capsule group (P<0.05). VEGF expression in each group reduced.Conclusion:The treatment of tonifying the kidney and activating the blood could positively regulate the angiogenesis of the ischemic cerebral tissue and the surrounding tissue by regulating the VEGF-Notch/Delta cascade signaling pathway so as to nourish and repair the damaged neuron and effectively improve the cognitive impairment induced by the cerebral ischemia. |
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