富含半胱氨酸蛋白61和血管内皮生长因子在大脑中动脉慢性闭塞性病变患者体内表达水平和相互作用研究  

Expression and interaction of cysteine-rich protein 61 and vascular endothelial growth factor in patients with chronic occlusion in middle cerebral artery

作　　者：刘洋[1] 王英 梁咏涵 王广瑜 王丹丹 李春燕 邱峰 Liu Yang;Wang Ying;Liang Yonghan;Wang Guangyu;Wang Dandan;Li Chunyan;Qiu Fen(Department of Neurology,the Second Affiliated Hospital of Qiqihar Medical College,Qiqihar,Heilongjiang 161006,China)

机构地区：[1]齐齐哈尔医学院附属第二医院神经内科,161006 [2]解放军总医院第一医学中心神经内科医学部

出　　处：《中国脑血管病杂志》2022年第10期677-684,共8页Chinese Journal of Cerebrovascular Diseases

基　　金：黑龙江省省属高等学校基本科研业务费科研项目(2021-KYYWF-0376);齐齐哈尔医学科学院临床科研基金资助项目(QMSI2019L-13)。

摘　　要：目的探索富含半胱氨酸蛋白61(CYR61)和血管内皮生长因子(VEGF)在大脑中动脉慢性闭塞性病变患者体内的表达水平及调控关系。方法回顾性连续纳入2018年6月至2021年10月在齐齐哈尔医学院附属第二医院脑血管狭窄诊断与介入治疗中心诊治的40例大脑中动脉慢性闭塞性病变患者并进入试验组,依据全脑血管造影显示的侧支代偿情况,将试验组患者分为2组,其中二级侧支代偿组29例,二级+三级侧支代偿组11例,并收集同期于齐齐哈尔医学院附属第二医院神经内科住院的20例无脑动脉狭窄的缺血性卒中患者并进入对照组。入组患者或其家属签署知情同意书后,采集静脉血,利用实时荧光定量聚合酶链式反应(PCR)技术分析CYR61和VEGF(VEGFA、VEGFB、VEGFC、VEGFD)在患者体内的表达规律,并利用细胞转染和双荧光素报道基因实验探索CYR61与VEGF之间的调控关系。通过GeneMANIA数据库(http://genemania.org/)对CYR61与VEGFA的相互作用进行预测,基因和基因作用的位点(序列)通过Match-1.0 Public软件分析。结果二级+三级侧支代偿组CYR61和VEGFA的表达水平均高于二级侧支代偿组和对照组(均P<0.01),二级侧支代偿组CYR61和VEGFA的表达水平与对照组差异无统计学意义(均P>0.05)。而VEGFB、VEGFC和VEGFD在实验组与对照组之间表达水平差异均无统计学意义(均P>0.05)。经http://genemania.org/数据库结构预测和Match-1.0 Public软件作用位点分析,血小板反应蛋白1(THBS1)可能是CYR61调控VEGFA的关键因子,且在二级+三级侧支代偿组中THBS1表达水平高于二级侧支代偿组和对照组(均P<0.01),其表达趋势与CYR61和VEGFA基本一致。进一步的双荧光素报道基因试验表明,CYR61可通过血清应答因子(SRF)增强THBS1的表达,相对值达到5.63;THBS1可通过调控因子X1(RFX1)增强VEGFA的表达,相对值达到2.67。结论CYR61和VEGFA在启动二级+三级侧支循环的大脑中动脉慢性闭�Objective To explore the expression and regulatory of cysteine-rich protein 61(CYR61)and vascular endothelial growth factor(VEGF)in patients with chronic occlusion in middle cerebral artery(MCA).Methods Forty patients with chronic occlusion in MCA were collected as the experimental group from the cerebrovascular stenosis diagnosis and interventional therapy center of the Second Affiliated Hospital of Qiqihar Medical College from June 2018 to October 2021,including 29 patients in the secondary collateral circulation group and 11 patients in the secondary and tertiary collateral circulation group.Twenty patients without new ischemic stroke were collected as the control group during the same period in the Department of Neurology,the Second Affiliated Hospital of Qiqihar Medical College.After the patients or their families signed the informed consent,venous blood was collected.The expression of CYR61,VEGF(VEGFA,VEGFB,VEGFC,VEGFD)and THBS1(thrombospondin1)genes in patients was analyzed by real-time quantitative polymerase chain reaction(qPCR)technology,and the regulatory relationship between CYR61,THBS1 and VEGF was explored by cell transfection and double fluorescein reporter gene experiments.The interaction between CYR61 and VEGFA was predicted by the GeneMANIA database(http://genemania.org/),and the gene action sites(sequences)were analyzed by Match-1.0 Public.Results The expression levels of CYR61 and VEGFA in the secondary and tertiary collateral compensation group were higher than those in the secondary collateral compensation group and the control group(all P<0.01),and the expression levels of CYR61 and VEGFA in the secondary collateral circulation group were not significantly different from those in the control group(all P>0.05).The expression levels of VEGFB,VEGFC and VEGFD between the experimental group and the control group were not statistically significant(all P>0.05).According to the prediction result of the GeneMANIA database and Match-1.0 Public,THBS1 is the key factor of CYR61 regulating VEGFA.The exp

关 键 词：大脑中动脉 闭塞 侧支循环 富含半胱氨酸蛋白质61 血管内皮生长因子 血小板反应蛋白1 

分 类 号：R743.3[医药卫生—神经病学与精神病学]