静脉血栓栓塞症的维医"同病异证"机理及其与炎症相关基因多态性的关联性研究

Venous thromboembolism (VTE) is a multidisciplinary-involved disease which is very common and fatal, and it’s been also recognized as a international health care issue whose pathogenesis remain to be clear. Recently people began to focus on the role of inflammatory factors in the pathogenesis of VTE. Inspired from the idea of abnormal hilit types according to traditional Uyghur medicine, we intend to indicate the genetic susceptibility of VTE, which also provides the possibilities that diagnoses could be made on the basis of genetic information. In this study, we are planning to classify VTE patients into different groups based on the theory of abnormal hilit types and investigate the association between the expression of inflammatory cytokines and abnormal hilit types. In the light of our previous work, TaqMan genotyping analysis would be used to investigate the correlation between inflammatory cytokine gene polymorphisms and different hilit types, and then we will detect the function of the important correlation gene polymorphisms. Further we will search for genetic markers of susceptibility genes, and set a comprehensive explanation for the pathogenesis of VTE from the gene-protein-environmental to provide a theoretical basis to the etiology of VTE and also a new target to individualized treatment.

静脉血栓栓塞症（VTE）是一种涉及诸多学科和领域的常见病，发病率高且逐年上升；病因复杂且发病机制尚未阐明，需要从不同角度揭示其奥秘和规律。维医对血栓栓塞性疾病有一定的理论基础和治疗优势。根据维医体液论，异常黑胆质是血栓栓塞性疾病的主要证型。课题组前期研究表明异常黑胆质证具有心、脑血管等复杂性、难治性血栓栓塞性疾病的生物学基础紊乱状态共性；VTE的发生可能与炎症因子及其遗传变异密切关联。本研究拟对VTE患者进行维医异常体液分型，研究VTE发生与不同异常体液质分型的关系；同时选择较为公认的炎症易感基因指标，采用TaqMan基因分型技术，研究不同异常体液质型与候选易感基因多态性的关系，继而通过关键基因的强关联SNP功能研究，探讨VTE发生、不同异常体液质型和遗传易感性三者关系，为揭示VTE维医“同病异证”理论及个体化临床治疗提供科学依据。

静脉血栓栓塞症（venous thromboembolism，VTE）的发病与炎症免疫相关基因多态性的关联机制越来越引起关注，炎性因子基因多态性可能通过影响自身及其他炎性细胞因子的表达水平及生物学活性，导致VTE的发生、发展。维吾尔医学（维医）对血栓栓塞性疾病有独特的认识和有效的疗法。已有研究证实，异常沉液质证具有心、脑血管等复杂性、难治性血栓栓塞性疾病的生物学基础紊乱状态共性；冠心病、高血压等复杂性疾病的异常沉液质证患者血栓前状态改变更明显；异常沉液质形成后，可能在血管壁产生沉淀，刺激血管壁，激活一系列凝血过程最终导致血栓形成。本研究首先建立了新疆地区VTE血样本及基因库,对VTE组及对照组进行了维医体液分型，结果提示：VTE组体液分布以异常沉液质型（42.0%）为主，与对照组比较，血浆纤维蛋白原、D-二聚体、纤溶酶原激活物抑制物-1和组织型纤溶酶原激活物等血栓标志物和白细胞介素-6、C-反应蛋白、肿瘤坏死因子-a等炎症标志物水平在异常沉液质组更高（P＜0.05），提示异常沉液质体液可能导致人体凝血功能紊乱，激活炎症系统，从而参与VTE的发生、发展。与对照组比较，非特异性炎症标志物白细胞介素-1，血清淀粉样蛋白A，IL-6，TNF-a水平在VTE组明显升高，提示VTE患者体内存在炎症反应激活状态。本研究检测了VTE组和对照组IL-1、SAA、IL-6和TNF-a基因分型和危险因素分析，结果显示，IL-1 rs2234650基因突变是VTE的危险因素（OR=2.086，P＜0.05），IL-1 rs1800587基因突变是VTE的保护因素（OR=0.226，P＜0.05）。研究结果表明，异常沉液质型体液、炎症激活，炎症基因突变可能与VTE发生、发展密切相关。本项目从维医体液分型，炎症标志物及其基因多态性三位一体的角度揭示了VTE发生、发展机制，为VTE的防治提供了新思路，新靶点。依托本项目，课题组共发表核心期刊论著6篇，SCI论著1篇，已培养硕士研究生和博士研究生各1名，正在培养博士研究生1名，后续研究结果待陆续发表。