【摘要】：研究背景及目的：腹主動脈瘤是多因素相互作用的結果,其顯著病理學特點是炎癥和動脈粥樣硬化。研究發(fā)現(xiàn)一些生物學標記物與腹主動脈瘤相關,但是哪一個標記物是診斷腹主動脈瘤的最佳指標,目前沒有共識。動物實驗研究已經(jīng)證實Notch信號在腹主動脈瘤發(fā)病機制中起重要作用。腹主動脈瘤患者血中的Notch配體,Notch受體和α腫瘤壞死因子轉(zhuǎn)移酶(TACE)還沒有被檢測過。本研究首次檢測腹主動脈瘤患者血漿Jagged1, Notch受體和TACE,研究其與腹主動脈瘤的關系,是否是診斷腹主動脈瘤的可靠生物學標記物。實驗方法：入組42例腹主動脈瘤患者和36例非腹主動脈瘤患者。對兩組的主動脈直徑和臨床危險因素進行比較。酶聯(lián)免疫吸附試驗(ELISA)檢測兩組患者血漿Jagged1, Notch受體(Notch 1-4)和TACE濃度。通過Logistic回歸和受試者操作曲線(ROC)分析血漿Notch1和TACE在診斷AAA中的價值。免疫熒光共定位Notch 1和TACE在腹主動脈瘤組織的表達。結果：腹主動脈瘤組血漿Notch1和TACE濃度明顯高于對照組(Notch 1,177.3±19.84 pg/ml vs.109.8 ± 5.68 pg/ml, P=0.001; TACE,2395±259.0 pg/ml vs.1113±215.2 pg/ml, P0.0001) 。通過分析ROC曲線下而積(area under the curve, AUC),血漿Notch1診斷腹主動脈瘤的AUC是0.878(95% CI0.771 to 0.985,P0.0001)TACE診斷腹主動脈瘤的AUC是0.804(95% CI0.669 to 0.94,P=0.001)。聯(lián)合檢測Notch1和TACE能夠提高診斷腹主動脈瘤的準確性(AUC 0.984,95%CI 0.955 to1.013,P0.0001)。二者聯(lián)合檢測的預測可能性界值0.7的敏感性是90.5%,特異性達到100%。免疫熒光共定位發(fā)現(xiàn)Notch1和TACE在腹主動脈瘤組織高表達,且主要分布在CD68+巨噬細胞。結論：本研究首次發(fā)現(xiàn)Notch1和TACE腹主動脈瘤血漿中高表達。Notch1和TACE是診斷腹主動脈瘤的可靠生物學標記物。聯(lián)合檢測Notch1和TACE能夠提高診斷的敏感性和特異性。同時也證實了Notch信號在腹主動脈瘤發(fā)病中的作用,該通路可以作為治療的靶點。
[Abstract]:Background and objective: abdominal aortic aneurysm is the result of multifactor interaction, and its significant pathological features are inflammation and atherosclerosis. Some biological markers have been found to be associated with abdominal aortic aneurysm, but there is no consensus as to which marker is the best index for the diagnosis of abdominal aortic aneurysm. Animal experimental studies have confirmed that Notch signal plays an important role in the pathogenesis of abdominal aortic aneurysm. Notch ligands, Notch receptors and 偽 tumor necrosis factor transferase (TACE) have not been detected in the blood of patients with abdominal aortic aneurysm. In this study, the relationship between plasma Jagged1, Notch receptor and TACE, in patients with abdominal aortic aneurysm and abdominal aortic aneurysm was detected for the first time, and whether it was a reliable biological marker for the diagnosis of abdominal aortic aneurysm. Methods: 42 patients with abdominal aortic aneurysm and 36 patients with non-abdominal aortic aneurysm were enrolled in the study. The aortic diameter and clinical risk factors were compared between the two groups. Plasma Jagged1, Notch receptor (Notch 1 鈮，

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