单纯创伤性脑损伤患者凝血因子Ⅶ启动子区甲基化及其与进展性颅内出血的相关性研究  

Promoter methylation of coagulation factor Ⅶ in patients with traumatic brain injury and its association with intracranial progressive hemorrhagic injury

作　　者：卢香琼 吴惺 袁强 吴思荣[1] 路鑫[1] 毛颖 周良辅 胡锦 Lu Xiangqiong;Wu Xing;Yuan Qiang;Wu Sirong;Lu Xin;Mao Ying;Zhou Liangfu;Hu Jin(Department of Emergency Medicine, First Affiliated Hospital of Soochow University, Suzhou 215006, China)

机构地区：[1]苏州大学附属第一医院急诊医学科,江苏省苏州市215006 [2]复旦大学附属华山医院神经外科

出　　处：《中华创伤杂志》2018年第4期289-292,共4页Chinese Journal of Trauma

基　　金：国家自然科学基金（81000518,81171133,81271375）;国家重点基础研究发展计划（2009CB941100,2010CB945500,2012CB966300）

摘　　要：目的研究单纯创伤性脑损伤（TBI）患者血浆凝血因子Ⅶ（FⅦ）启动子区甲基化水平与FⅦ活性（FⅦa）的关系，探讨FⅦ启动子区甲基化与进展性颅内出血（PHI）的相关性。方法采用前瞻性队列研究分析2010年8月-2014年8月急诊入院的79例单纯TBI患者的临床资料。采集患者入院时外周静脉血并送检FVHa，提取患者血液DNA，检测FⅦ启动子区CpG2、CpG3、CpG4、CpG5、CpG6甲基化率。根据患者血浆FVHa水平，将患者分为FⅦa≥90％组和FVHa〈90％组；根据患者是否存在PHI，将患者分为PHI组和非PHI组。比较四组患者FⅦ启动子区CpG各位点甲基化率、性别、年龄、收缩压、格拉斯哥昏迷评分（GCS）、住院时间及病死率。结果四组患者性别、年龄、收缩压、GCS、住院时间和病死率差异均无统计学意义（P均〉0．05）。FⅦa≥90％组患者CpG3位点甲基化率小于FVHa〈90％组（0．83±0．05：0．85±0.03）（P〈0．05），而两组患者CpG2、CpG4、CpG5、CpG6等位点甲基化率差异无统计学意义（P〉0．05）。PHI组与非PHI组患者以上CpG各位点甲基化率差异无统计学意义（P〉0．05）。结论单纯TBI患者FⅦ基因启动子区甲基化率与血浆FVHa水平相关，甲基化率高，患者血浆FVHa水平低；而FⅦ启动子区甲基化率与患者是否发生PHI无相关性。Objective To study the effect of the promoter methylation of coagulation factor Ⅶ （FⅦ） on the coagulation factor Ⅶ activity （FⅦa） in traumatic brain injury （TBI） patients, and the correlation between the promoter methylation in FⅦ and intracranial progressive hemorrhagic injury （PHI）. Methods A prospective analysis was conducted on 79 patients with moderate-severe TBI admitted to emergency department from August 2010 to August 2014. The peripheral venous blood samples were collected at admission and then were delivered for measurement of FVIIa. Genomic DNA was isolated from patient blood, and the promoter methylation in FⅦ （ CpG2, CpG3, CpG4, CpGS, and CpG6） were analyzed. According to the level of plasma FⅦa, the patients were divided into FⅦa H 90% group and FⅦa 〈90% group. Based on the presence of PHI, the patients were divided into PHI group and non-PHI group. The FVII promoter methylation, age, gender, systolic blood pressure, Glasgow Coma Scale （GCS）, length of stay and mortality between FⅦa≥90% group and FⅦa 〈90% group, PHI group and non-PHI group were compared. Results There were no significant differences in age, gender, systolic blood pressure, GCS, LOS, and mortality between FⅦa 1〉90% group and FVIIa 〈 90%, PHI group and non-PHI group （P 〉 0. 05）. The methylation of CpG3 in FⅦa ≥90% group was less than that in FVlIa 〈90% group （ 0.83 ±0.05 vs. 0.85 ±0.03） （P〈0.05）, while there were no significant differences in other CpG sites between these two groups （ P 〉 0.05 ）. No significant differences in all of methylation levels of the CpG sites between PHI group and non-PHI group were found （P 〉 0. 05 ）. Conclusions The promoter methylation of FⅦ affects plasma FⅦa concentrations, and higher methylation results in lower FⅦa. The promoter methylation of FⅦ is not associated with PHI in TBI patients.

关 键 词：脑损伤 因子Ⅶ 甲基化 进展性颅内出血 

分 类 号：R651.15[医药卫生—外科学]