白藜芦醇对化疗后脑胶质瘤动物模型血液高凝的影响及作用机制  

Effects of resveratrol on blood hypercoagulability in glioma animal model after chemotherapy by regulating Wnt pathway and its mechanism

作　　者：常娜[1] 陈超[3] 赵萌 张蕊 李博[2] Chang Na;Chen Chao;Zhao Meng;Zhang Rui;Li Bo(Department of Radiotherapy and chemotherapy,Tangshan Municipal People's Hospital,Tangshan,Hebei 063000,China;Department of Pharmacy,Tangshan Municipal People's Hospital,Tangshan,Hebei 063000,China;Department of Pathology,Zunhua People's Hospital,Zunhua Hebei,064200,China)

机构地区：[1]唐山市人民医院唐山市肿瘤放射治疗学重点实验室,河北唐山063000 [2]唐山市人民医院药剂科,河北唐山063000 [3]遵化市人民医院病理科,河北遵化064200

出　　处：《中国微侵袭神经外科杂志》2023年第12期169-173,共5页Chinese Journal of Minimally Invasive Neurosurgery

基　　金：河北省2019年度医学科学研究课题计划(编号:20191618)。

摘　　要：目的为探究白藜芦醇(Resveratrol,RSV)对化疗后脑胶质瘤动物模型血液高凝的影响及作用机制。方法通过皮下注射U87细胞构建小鼠胶质瘤动物模型,将建模成功的小鼠随机分为3组(每组5只):对照组、替莫唑胺(temozolomide,TMZ)组和TMZ+RSV组。其中TMZ组和TMZ+RSV组使用TMZ灌胃,剂量为50mg/(kg·d)。TMZ+RSV组小鼠用RSV灌胃,剂量10mg/(kg·d)。分析RSV对肿瘤生长和血液高凝状态的影响。通过Western blot检测肿瘤和血管内皮组织中Wnt通路水平。结果TMZ组肿瘤体积(144.56±15.24)mm3和质量(114.11±13.07)mg,均显著低于对照组(P<0.05);TMZ+RSV组肿瘤体积(106.45±13.15)mm3和质量(90.23±10.38)mg,均显著低于TMZ组(P<0.05)。对照组肿瘤组织中细胞凋亡率为(4.16±1.05)%,TMZ组凋亡率为(15.83±2.54)%,显著高于对照组(P<0.05);TMZ+RSV组凋亡率为(24.03±3.85)%,显著高于TMZ组(P<0.05)。TMZ组全血黏度、PT、APTT和ET1显著高于对照组,NO低于对照组(P<0.05)。TMZ+RSV组全血黏度、PT、APTT和ET1显著低于TMZ组,NO高于TMZ组(P<0.05)。对照组和TMZ组肿瘤和血管内皮组织中Wnt2和β-catenin比较,差异不显著(P>0.05),TMZ+RSV组肿瘤组织和血管内皮组织中Wnt2和β-catenin显著低于对照组和TMZ组(P<0.05)。结论RSV可通过抑制肿瘤组织和血管内皮细胞中Wnt通路,促进肿瘤细胞凋亡和保护血管内皮功能,缓解高凝状态。Objective To investigate the effect and mechanism of Resveratrol(RSV)on blood hypercoagulation in glioma animal model after chemotherapy by regulating Wnt pathway.Methods An animal model of mouse glioma was constructed by subcutaneous injection of U87 cells.The successfully modeled mice were randomly divided into 3 groups:control group(n=5),temozolomide(TMZ)group(n=5)and TMZ+RSV group(n=5).TMZ group and TMZ+RSV group were given TMZ intragastrically with a dose of 50mg/(kg·d).TMZ+RSV group were intervened by RSV.To analyze the effect of RSV on tumor growth and body hypercoagulability state.The level of Wnt pathway in tumor and vascular endothelial tissue was detected by Western blot.Results The tumor volume(144.56±15.24)mm3 and mass(114.11±13.07)mg in TMZ group were significantly lower than control group(P<0.05).Tumor volume(106.45±13.15)mm3 and mass(90.23±10.38)mg in TMZ+RSV group were significantly lower than TMZ group(P<0.05).The apoptosis rate of tumor tissue in control group was(4.16±1.05)%,and that in TMZ group was(15.83±2.54)%,which was significantly higher than that in control group(P<0.05).The apoptosis rate of TMZ+RSV group was(24.03±3.85)%,which was significantly higher than that of TMZ group(P<0.05).Whole blood viscosity,PT,APTT and ET1 in TMZ group were significantly higher than those in control group,while NO was lower than that in control group(P<0.05).Whole blood viscosity,PT,APTT and ET1 in TMZ+RSV group were significantly lower than those in TMZ group,while NO was higher than that in TMZ group(P<0.05).There was no significant difference in Wnt2 andβ-catenin in tumor and vascular endothelial tissue between control group and TMZ group(P>0.05),but Wnt2 andβ-catenin in tumor and vascular endothelial tissue of TMZ+RSV group were significantly lower than those of control group and TMZ group(P<0.05).Conclusions RSV can promote tumor cell apoptosis and protect vascular endothelial function by inhibiting the Wnt pathway in tumor tissues and vascular endothelial cells,and alleviate the hypercoagu

关 键 词：神经胶质瘤 替莫唑胺 白藜芦醇 WNT通路 高凝状态 

分 类 号：R730.264[医药卫生—肿瘤]