首页> 中文期刊> 《实用药物与临床》 >齐墩果酸通过VEGF-Src通路对蛛网膜下腔出血大鼠模型血管内皮紧密连接表达的影响

齐墩果酸通过VEGF-Src通路对蛛网膜下腔出血大鼠模型血管内皮紧密连接表达的影响

             

摘要

目的 探讨齐墩果酸对蛛网膜下腔出血后早期脑损伤的保护作用,阐释其可能的机制.方法 54只成年雄性SD大鼠分成3组(假手术组、SAH模型组、齐墩果酸给药组),每组18只.采用颈内动脉穿刺法建立大鼠SAH模型,造模1h后给药,24 h后进行神经功能损伤评分;检测脑水含量及脑伊文思蓝浸出;并利用Western blot方法检测脑组织Src、VEGF、ZO-1、Claudin-5、Occludin蛋白的表达量.结果 齐墩果酸高剂量给药可有效改善神经功能损伤(p<0.01);降低脑组织含水量和脑血管通透性(P<0.01);增加ZO-1、Claudin-5、Oc-cludin蛋白的表达,降低VEGF水平,抑制Src激活(P<0.05).结论 齐墩果酸对SAH后早期脑损伤有显著的保护作用,可改善脑水肿,其作用机制可能与增加脑组织紧密连接蛋白的表达有关.%Objective To explore the effect of oleanolic acid (OA) on early brain injury following subarachnoid hemorrhage (SAH) and explain its possible mechanism.Methods Totally 54 male SD rats were divided into 3 groups:sham group (n =18),SAH group (n =18) and OA-treated SAH group (n =18).The endovascular puncture model was used to induce SAH.Neurological score,brain water content and blood-brain barrier (BBB) were evaluated at 24 h after SAH.The protein expression of ZO-1,VEGF and Src was determined by Western blot.Results Highdose OA administration could significantly improve the neurological scores (P < 0.01),reduce the brain water content and BBB permeability (P < 0.01),up-regulate the expression of ZO-1,Claudin-5 and Occludin,and inhibit the expression of VEGF and Src phosphorylation (P < 0.01).Conclusion OA can protect against the early brain injury after SAH and improve brain edema by increasing the expression of tight junctions.

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