正文:摘要 目的:通过观察大脑中动脉闭塞(MCAO)大鼠血浆TAT、F1+2、D-二聚体、vWF含量的动态变化,探讨MCAO大鼠缺血后血栓生物标记物的变化规律,为药物研究确定最佳观察时间点。方法:雄性SD大鼠56只,随机分为:假手术组,缺血后不同时相组(1h、6h、12h、24h、48h、72h),每组8只。线栓法制造大脑中动脉闭塞大鼠模型,用ELISA法检测大鼠血浆TAT、F1+2、D-二聚体、vWF的水平。结果:脑缺血后1h TAT的水平即上升且于24h达峰值; F1+2、D-二聚体的水平在缺血后1h骤然升高并于6h达峰值; 而vWF在缺血后1h即骤然升高达峰值,然后维持在稳定的较高水平。结论:MCAO大鼠在急性脑缺血后血浆TAT、D-二聚体、vWF、F1+2水平均升高,表现出不同的时程规律,它们的峰值均集中在缺血后6h或24h,提示脑缺血的早期即存在有凝血纤溶系统紊乱、血管内皮细胞损伤,缺血后24h可作为药物研究的最佳观察时间点。
关键词:大脑中动脉闭塞;TAT;F1+2;D-二聚体;vWF
[基金项目]国家自然科学基金资助项目(81373508);湖南省教育厅项目(12A105);湖南省中医药管理局科研基金项目(201319);湖南省重点学科中西医结合基础资助项目;湖南省自然科学创新群体基金;湖南省高校科技创新团队;
通讯作者:李定祥(1968-),男,湖南临湘人,副教授,硕士研究生导师,主要从事五脏血瘀证的实质研究。E-mail:ldxlzy@hotmail.com。通讯地址:湖南省长沙市岳麓区含浦科教园区象嘴路;邮编:410208。
第一作者:刘文华,女,湖南中医药大学2012级硕士研究生,研究方向:中医药对脑血管疾病的研究。
The changes of plasma TAT、F1+2、D-dimer、vWF in the MCAO rats at different time points
Liu Wen-hua,Deng Yi-hui,Wen Guo,Qin Hong-yu,Li Ping,Li Ding-xiang
(Hunan University of Chinese Medicine Key Laboratory of Hunan Province for Prevention and Treatment of Integrated Traditional Chinese and Western Medicine on cardio-cerebral diseases, Key Laboratory of Hunan Universities for Cell biology and Molecular techniques ,Changsha, Hunan 410208).
Abstract Objective: Through the observation of dynamic changes of plasma TAT, F1+2, D- dimer, vWF content in the middle cerebral artery occlusion (MCAO) model rats, to discuss the change rules of thrombus biomarkers in MCAO model rats after ischemia, and determine the best observation time for drug research. Methods: All 56 male SD rats were randomly divided into sham-operated group and different ischemia groups(post-ischemia 1h、12h、6h、24h、48h、72h group),8 rats in each group .Rat model of middle cerebral artery occlusion was established first, and then elisa mehod was used to detect the levels of plasma TAT、F1+2、D-dimer、vWF in rats. Result: The levels of plasma TAT began to increase 1 hour after ischemia and reached the peak at the 24th hour ; the levels of plasma F1+2、D-dimer increased rapidly 1 hour after ischemia and reached the peak at the 6th hour ; while the levels of plasma vWF suddenly rose up to the peak 1 hour after ischemia, and then maintained at a stable high level. Conclusion: The levels of plasma TAT、F1+2、D-dimer、vWF all increased after ischemia in MCAO rats, showing different rules, while most peak appeared at 6th or 24th hour,suggesting that there were coagulation fibrinolytic system disorders and vascular endothelial cell injury during the early cerebral ischemia , 24th hour could be used as the best observation time point for drug research.
Key words: MCAO;TAT;F1+2;D-dimer;vWF