芹菜素通过VEGF通路对大脑中动脉阻塞后大鼠脑缺血半暗带血管神经再生的影响  

Effect of Apigenin on angiogenesis and neurogenesis in the cerebral ischemic penumbra of middle cerebral

作　　者：刘婵[1] 胡权 谢庆凤 朱安奇 陈翔[1] LIU Chan;HU Quan;XIE Qingfeng;ZHU Anqi;CHEN Xiang(Department of Children Rehabilitation,the Second Affiliated Hospital&Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou 325000,China)

机构地区：[1]温州医科大学附属第二医院育英儿童医院儿童康复科,浙江温州325000

出　　处：《温州医科大学学报》2023年第3期182-188,共7页Journal of Wenzhou Medical University

基　　金：温州市基础性科研项目(Y2020958)。

摘　　要：目的:探讨芹菜素促大脑中动脉阻塞(MCAO)后大鼠脑缺血半暗带血管生成和神经再生的作用,以及是否与血管内皮生长因子(VEGF)信号通路有关。方法:将144只SD大鼠分为假手术组(S7、S14)、模型组(M7、M14)、芹菜素模型组(AM7、AM14)和芹菜素+VEGF受体(VEGF-R)抑制剂模型组(AIM7、AIM14)。构建MCAO模型后,采用改良神经行为学评分(mNSS)和TTC染色评估神经功能和脑梗死体积,采用Western blot、免疫组化和免疫荧光评估脑缺血半暗带中VEGF表达水平以及血管生成和新生神经元的变化。结果:与S组比较,M组、AM组和AIM组均出现不同程度的神经行为学异常和白色梗死灶,AM组较同期M组的mNSS评分降低、脑梗死体积减小(P<0.05);缺血半暗带AM组与同期M组比较VEGF表达增加(P<0.01),AM7组较M7组的脑微血管密度增高(P<0.05);AM7组BrdU/Nestin和AM14组BrdU/NeuN的双标阳性细胞数目均较同期M组明显升高(P<0.01);但VEGF-R抑制剂均可下调芹菜素的上述作用。结论:芹菜素可通过上调VEGF信号通路促进脑缺血半暗带血管生成和神经再生,改善局灶性脑缺血再灌注所致的神经功能缺损。Objective:To investigate the effects of Apigenin(APG)-induced angiogenesis and neurogenesis in the cerebral ischemic penumbra of middle cerebral artery occlusion(MCAO)rats and whether these changes involve the vascular endothelial growth factor(VEGF)signaling pathway.Methods:A total of 144 adult male Sprague Dawley rats were randomly divided into sham operation group(groups S7 and S14,respectively),a model group(groups M7 and M14,respectively),an APG treatment model group(groups AM7 and AM14,respectively),and an APG+VEGF-R inhibitor treatment model group(groups AIM7 and AIM14,respectively).A MCAO animal model was established;neurobehavioral performance and infarct volumes were assessed using the modified neurological severity score(mNSS)and 2,3,5-triphenyl tetrazolium chloride staining;VEGF expression levels,and changes in angiogenesis and new neurons in the cerebral ischemic penumbra were evaluated using Western blot analysis,immunohistochemistry,and immunofluorescence.Results:Compared with the S group,the neurologic impairment symptoms and white infarcts were observed in the M group,AM group and AIM group;the neurological scores and infarct volume in the AM group were significantly decreased compared with those in the M group at the same time-point(P<0.05).The VEGF expression in the AM group was increased compared with that in the M group at the same time-point(P<0.01),and microvessel density was increased in the AM7 group compared with that in the M7 group(P<0.05).The number of bromodeoxyuridine(BrdU)/nestin and BrdU/NeuN double-labeled positive cells in the AM group were significantly increased compared with those in the M group at the same time-point(P<0.01).VEGF-R inhibitors reversed the improvement effect of APG.Conclusion:APG ameliorates focal cerebral ischemia/reperfusion-induced neurological deficit by promoting angiogenesis and neurogenesis through upregulation of the VEGF signaling pathway.

关 键 词：芹菜素 大脑中动脉阻塞 血管内皮生长因子 血管生成 神经再生 

分 类 号：R363[医药卫生—病理学]