背景:主动脉夹层是指主动脉介质的分离并沿长轴延伸以形成主动脉壁的真腔和假腔。65-70%的病人死于心脏填塞,心律失常,夹层破裂,等。目前,超声心动图,计算机断层扫描血管造影(CTA),等。是主动脉夹层的主要诊断工具。迄今为止,目前尚无可用于鉴别诊断和风险评估的快速血清分子标志物。目的:系统地筛选主动脉夹层和急性冠脉综合征患者血清分子标志物,初步确定急性主动脉夹层的发病机制。方法:对所有医院的相关纠纷案例进行AAD医疗纠纷比例的统计分析,2013年至2017年广东省医疗纠纷协调委员会数据库的早期死亡率和误诊率。血清和主动脉组织样本分别通过iTRAQ和无标记分析进行定量,对2016-2018年南方医科大学珠江医院和广东省人民医院的AAD和对照患者进行了进一步的ELISA和免疫荧光和Westernblot验证。结果:150例心血管纠纷中,AAD病例占15.29%,所有心血管病死亡少于24h的59.26%,死亡时仍未确诊的患者占88.89%,84种蛋白质(66和18种上调和下调,分别)通过iTRAQ和16种蛋白质(9种和7种上调和下调,分别)通过无标签。九种蛋白质(Lumican,FGL1,PI16,MMP9,FBN1,MMP2,VWF,通过David/Ease和String技术将与主动脉夹层发病机制相关的MMRN1和PF4)鉴定为用于验证测试的候选生物标志物。四种蛋白质(Lumican,ELISA验证后发现FGL1、PI16、MMP9)有统计学差异。除Lumican外,FGL1,PI16和MMP9蛋白的表达在病理上显着增加。组织学上,TGF-β1,α-SMA,主动脉组的胶原蛋白1也显著高于主动脉组。结论:Lumican,FGL1、PI16和MMP9可能是AAD患者的潜在生物标志物,Lumican介导的TGF-β1通路可能参与了主动脉夹层的发病机制。
Background: Aortic dissection refers to the separation of aortic media and extension along the long axis to form the true and false chambers of the aortic wall. 65-70% of the patients died of cardiac tamponade, arrhythmia, dissection rupture, etc. At present, echocardiography, computed tomography angiography (CTA), etc. are the main diagnosis tools for aortic dissection. To date, there is no rapid serum molecular marker that can be used for differential diagnosis and risk assessment. Objectives: To screen serum molecular markers systematically amid aortic dissection and acute coronary syndrome and to preliminarily identify the pathogenesis of acute aortic dissection. Methods: Related disputes cases of all hospitals were statistically analyzed for the AAD medical disputes ratio, early death ratio and misdiagnosis ratio from the database of Guangdong Province Medical Disputes Coordination Committee from 2013 to 2017. Serum and Aortic tissues samples were respectively quantified by iTRAQ and label-free analysis, further validated by ELISA and protein verified by immunofluorescence and Western blot from AAD and control patients enrolled from the Zhujiang Hospital of Southern Medical University and Guangdong Province people\'s Hospital from 2016 to 2018. Results: AAD cases ratio accounted for 15.29% in all 150 cardiovascular disputes, 59.26% in all cardiovascular death less than 24 h, and 88.89% in the patients who remained undiagnosed at the time of death, 84 proteins (66 and 18 upregulated and downregulated, respectively) were identified by iTRAQ and 16 proteins (9 and 7 upregulated and downregulated, respectively) by Label-free. Nine proteins (Lumican, FGL1, PI16, MMP9, FBN1, MMP2, VWF, MMRN1, and PF4) related to the pathogenesis of aortic dissection were identified by David /Ease and String techniques as candidate biomarkers for verification test. Four proteins (Lumican, FGL1, PI16, and MMP9) were found to be statistically different after ELISA verification. The expression of FGL1, PI16, and MMP9 proteins was pathologically significantly increased except for Lumican. Histologically, TGF-β1, α-SMA, and Collagen1 were also significantly higher in the aortic group. Conclusion: Lumican, FGL1, PI16, and MMP9 may be potential biomarkers in AAD patients, and the Lumican-mediated TGF-β1 pathway is likely to be involved in the pathogenesis of aortic dissection.