银杏二萜内酯葡胺基于Caveolin-1/VEGF通路对脑卒中大鼠脑中血管新生的影响  

Effect of Ginkgo diterpene lactone meglumine on cerebral angiogenesis in stroke rats through Caveolin-1/VEGF pathway

作　　者：王芳[1] 王瑶[1] 冯昌威 Wang Fang;Wang Yao;Feng Changwei(Department of Neurology,the Tieling Central Hospital,Liaoning 112000,China)

机构地区：[1]铁岭市中心医院神经内科,辽宁112000 [2]中国医科大学第一附属医院神经内科

出　　处：《脑与神经疾病杂志》2021年第11期693-698,共6页Journal of Brain and Nervous Diseases

基　　金：辽宁省自然科学基金项目(20170540569)。

摘　　要：目的探讨银杏二萜内酯葡胺对缺血性脑卒中大鼠脑中血管新生的影响及其机制。方法SD大鼠随机分为对照组,脑缺血-再灌注组,银杏二萜内酯葡胺组,银杏二萜内酯葡胺+血管内皮生长因子(VEGF)抑制剂组。各组大鼠进行脑缺血-再灌注造模并持续给药观察21d。给药结束后,采用行为学检测大鼠神经功能,2,3,5-三苯基氯化四氮唑(TTC)染色检测缺血侧梗死面积,免疫荧光检测半影区血管新生,Western blot检测血管新生相关蛋白表达。结果与对照组相比,脑缺血-再灌注造成大鼠神经功能评分升高(P<0.05),导致缺血侧出现显著梗死面积(P<0.05),且半影区高度糖基化的Ⅰ型跨膜糖蛋白/α-肌动蛋白(CD34/α-SMA)双阳性面积增加(P<0.05),此外,缺血侧脑组织小窝蛋白(Caveolin-1),血管内皮生长因子(VEGF),促血管生成素-1(Ang-1)表达增加(P<0.05)。与此同时,与脑缺血-再灌注组相比,银杏二萜内酯葡胺持续干预有效降低了大鼠神经功能评分(P<0.05),显著减少了缺血侧梗死面积(P<0.05),增加了大鼠缺血侧半影区CD34/α-SMA双阳性区域面积(P<0.05),进一步上调了缺血侧脑组织Caveolin-1,VEGF,Ang-1表达(P<0.05)。然而,与银杏二萜内酯葡胺组相比,VEGF抑制剂却显著降低了缺血侧脑组织Caveolin-1,VEGF,Ang-1表达(P<0.05),减少CD34/α-SMA双阳性区域面积(P<0.05),介导缺血侧梗死面积增加与神经功能评分升高(P<0.05)。结论银杏二萜内酯葡胺通过Caveolin-1/VEGF/Ang-1信号通路,促进血管新生,减少缺血区梗死面积并最终改善大鼠神经功能损伤。Objective To investigate the effect and mechanism of ginkgo diterpene lactone meglumine on cerebral angiogenesis in rats with ischemic stroke.Methods SD rats were randomly divided into Control(Con)group,Cerebral ischemia-reperfusion(I/R)group,Ginkgo diterpene lactone meglumine(GDLM)group,and Ginkgo diterpene lactone meglumine+Vascular endothelial growth factor(VEGF)inhibitor(GTLM+PD173074)group.Rats in each group were continuously treated with drugs after cerebral ischemia-reperfusion operation for 21 days.Behavior test was detected for neurological scores,2,3,5-Triphenyltetrazolium chloride(TTC)staining was performed for ischemic infarct area detections,immunofluorescence was applied for angiogenesis detection,and Western blot was employed for angiogenesis-related protein expression detection.Results Compared with Control group,Cerebral ischemia-reperfusion caused an increase in neurological scores(P<0.05),resulted in a chunk of infarct area in brain(P<0.05),and lead to an increase of CD34/α-SMA double positive area in the penumbra(P<0.05).In addition,the expressions of Caveolin-1,VEGF,and Ang-1 in the ischemic region up-regulated(P<0.05).Meantime,compared with I/R group,continuous administration of GDLM effectively decreased the neurological scores in rats(P<0.05),lead to a decrease of infarct area in brain(P<0.05),and significantly increased the area of the CD34/α-SMA double positive region in the penumbra(P<0.05).Furthermore,GDLM significantly upregulated the expression of Caveolin-1,VEGF,and Ang-1 in the ischemic region(P<0.05).However,compared with GDLM group,VEGF inhibitor significantly reduced the expression of Caveolin-1,VEGF,and Ang-1 in the ischemic region(P<0.05),reduced the area of the CD34/aα-SMA double positive area(P<0.05)and mediated the increase of infarct area and the neurological scores(P<0.05).Conclusion Ginkgo diterpene lactone meglumine promotes angiogenesis through Caveolin-1/VEGF/Ang-1 signaling pathway,reduces infarct area and ultimately improves neurological damage in rats.

关 键 词：银杏二萜内酯葡胺 缺血性脑卒中 大鼠 血管新生 血管内皮生长因子 

分 类 号：R743.32[医药卫生—神经病学与精神病学]