创伤性深静脉血栓形成早期诊断指标的筛选及其机制研究

From now, it is difficult to diagnose deep vein thrombosis in post-traumatic early.Our group has been concerned about post-traumatic deep vein thrombosis development for years. In our previous work, we have obtained a amount of key genes that relate to thrombus formation, development, regression and other states. The initial part of the process depicting thrombotic changes in the molecular level has also been achieved through bioinformatics analysis and part of the gene function query. However, protein is the ultimate enforcer of biological function, only genetic research still can not answer the questions of genetic translation, modification and other issues. To continue in-depth interpretation of the thrombosis, the development mechanism, and to achieve early diagnosis which is still difficult nowadays. It is necessary to do research at the protein level. Therefore, based on the previous study, proteomics method is introduced into studies of rat femoral vein vascular endothelial tissue to look for early warning indicators of traumatic deep vein thrombosis. To confirm the reliability, we do it in vivo and vitro experiments. We explore its relationship with thrombosis in order to get molecular markers of good specificity and high sensitivity and to provide scientific basis for early diagnosis of post-traumatic deep vein thrombosis.

国内外目前所用的检查方法难以对创伤后深静脉血栓形成进行早期诊断，本课题组多年来一直关注该领域的发展动态，前期工作中我们已经获得与血栓形成、发展、消退等各个状态相关的关键基因，通过生物信息学分析和基因功能查询，初步描绘出血栓部分过程中分子水平的变化。由于蛋白是生物功能最终执行者，仅从基因角度进行研究尚不能解决基因的翻译、修饰等问题，要继续深入诠释血栓发生、发展的机理，解决早期诊断困难的难题，有必要从蛋白层面进行研究。因此，本课题在前期研究的基础上，拟采用蛋白质组学方法对创伤性深静脉血栓大鼠股静脉血管内皮进行研究，以寻找能早期诊断创伤后深静脉血栓形成的预警指标。为确定其可靠性，更进一步从细胞水平、动物水平对差异表达蛋白进行功能验证，探讨其与血栓形成之间的关系，旨在获得特异性好、灵敏性高的分子标志物，为早期诊断创伤后深静脉血栓形成提供科学依据。

创伤后深静脉血栓形成发病率高、危害性大。由于发病机制尚未清楚，目前所用的检查方法未能对TDVT进行早期诊断，所以很多患者未能得到及时的诊治。本研究首次应用血清蛋白质组学技术对创伤性深静脉血栓形成进行研究，发现创伤后深静脉血栓形成与无血栓形成组相比，在血清蛋白质组成分中存在差异。经质谱鉴定差异表达蛋白为血清补体4α、视黄醇结合蛋白、补体因子B、谷胱甘肽过氧化物酶3前体、α- 2球蛋白前体、大鼠甲状腺素a链、serpin II、白蛋白、白介素17、白介素18、TGF-β1 和serpin II。这些差异蛋白质为进一步完善创伤后深静脉血栓形成血清学诊断指标提供了参考依据。其中，血清补体4α、补体因子B、白介素17、白介素18、TGF-β1 和serpin II与创伤后深静脉血栓形成早期诊断之间的相关性研究目前尚未见报道，初步验证结果提示其与创伤后深静脉血栓形成密切相关，可作为创伤后深静脉血栓形成早期辅助诊断的潜在血清标记物和可能存在的治疗靶点。