柚皮素对大龄脑缺血模型大鼠脑皮质微血管新生的影响  

The effect of naringenin on cerebral cortex microangiogenesis in aged rat model of cerebral ischemia

作　　者：王瑜 梁超 王宝爱 徐玉婷 Wang Yu;Liang Chao;Wang Baoai;Xu Yuting(Haikou Hospital of Traditional Chinese Medicine,Haikou 570216,China)

机构地区：[1]海南省海口市中医医院,570216

出　　处：《心脑血管病防治》2023年第8期22-26,共5页CARDIO-CEREBROVASCULAR DISEASE PREVENTION AND TREATMENT

基　　金：海南省自然科学基金项目(20158371)

摘　　要：目的研究柚皮素对大龄脑缺血模型大鼠缺血状态下脑皮质微血管新生和血管内皮细胞相关生长因子的影响。方法对100只鼠龄在20~24个月的大鼠进行脑缺血建模,按照随机数字表法分为空白组、对照组、低浓度组和高浓度组,每组各25只,对大鼠的缺血脑组织切片,分离培养脑微血管内皮细胞,实时荧光定量测量CXCL5、p38丝裂原活激活蛋白激酶(p38 MAPK)、血管内皮生长因子A(VEGFA)、血管内皮生长因子受体2(VEGFR2)及碱性成纤维细胞生长因子(bFGF)基因表达量,Western Blot检测各组VEGFA、VEGFR2、bFGF的蛋白表达量,划痕修复观察细胞迁移距离,倒置显微镜观察脑微血管内皮细胞迁移数目,免疫组化观察成管状况。结果与空白组比较,对照组、低浓度组、高浓度组p38 MAPK mRNA表达下调,CXCL5、VEGFA、VEGFR2、bFGF mRNA表达量明显上调(F=37.509、93.272、13.894、3.498、50.681,P<0.05)。与空白组比较,对照组、低浓度组、高浓度组VEGFA、VEGFR2、bFGF蛋白表达量增多(F=49.811、70.938、75.704,P<0.05)。与空白组相比,对照组、低浓度组、高浓度组脑血管内皮细胞迁移距离及迁移数目均增加(F=186.213、97.890,P<0.05)。与空白组相比,对照组、高浓度组和低浓度组的细胞成管数量均较高(F=52.291,P<0.05),且高浓度组脑血管内皮细胞成管能力明显高于对照组(P<0.05)。结论柚皮素可以上调大龄脑缺血模型大鼠脑血管内皮细胞中CXCL5、VEGFA、VEGFR2、bFGFmRNA表达,抑制细胞中p38MAPKmRNA表达,促进细胞迁移,加强成管,加快脑缺血组织血管新生。Objective To study the effects of naringin on cerebral cortical microangiogenesis and vascular endothelial cell-related growth factors in aged rat model of cerebral ischemia.Methods Cerebral ischemia modeling was performed in 100 rats aged 20 to 24 months,and they were divided into the blank group,control group,low-concentration group and high-concentration group according to a random number table,with 25 rats in each group.Cerebral microvascular endothelial cells were isolated and cultured from the sections of ischemic brain tissue of each group.The Gene expression levels of CXCL5 and p38 kinogen-activated protein kinase(p38 MAPK),vascular endothelial growth factor A(VEGFA),vascular endothelial growth factor receptor 2(VEGFR2)and basic fibroblast growth factor(bFGF)genes were quantitatively measured by real-time fluorescence.The protein expression levels of VEGFA,VEGFR2 and bFGF in each group were detected by Western Blot.The migration distance of cells was observed by scratch repair,and the migration number of cerebral microvascular endothelial cells was observed by inverted microscope.The tube formation was observed by immunohistochemistry.Results Compared to the blank group,the control group,low-concentration group and high-concentration group exhibited downregulated p38 MAPK mRNA,while showing significantly upregulated CXCL5,VEGFA,VEGFR2 and bFGF mRNA expression levels(F=37.509,93.272,13.894,3.498,50.681;P<0.05).Compared with the blank group,the protein expressions of VEGFA,VEGFR2 and bFGF mRNA in control group,low-concentration group and high-concentration group increased(F=49.811,70.938,75.704;P<0.05).Compared with the blank group,the migration distances and numbers of cerebral vascular endothelial cells in control group,low-concentration group and high-concentration group increased(F=186.213,97.890;P<0.05).Compared with the blank group,the numbers of tube-forming cells was higher in the control group,high-concentration group and low-concentration group(F=52.291,P<0.05),with the high-concentration group sh

关 键 词：柚皮素 CXCL5 p38丝裂原活激活蛋白激酶 微血管新生 

分 类 号：R285.5[医药卫生—中药学]