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肠屏障功能障碍:急性Stanford A型主动脉夹层炎症反应的新型治疗靶点

Intestinal Barrier Dysfunction: A Novel Therapeutic Target for Inflammatory Response in Acute Stanford Type A Aortic Dissection.

作者信息

Gu Jun, Hu Jia, Qian Hong, Shi Yingkang, Zhang Eryong, Guo Yingqiang, Xiao Zhenghua, Fang Zhi, Zhong Minghua, Zhang Hongwei, Meng Wei

机构信息

Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Cheng du, Sichuan, People's Republic of China.

Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Cheng du, Sichuan, People's Republic of China

出版信息

J Cardiovasc Pharmacol Ther. 2016 Jan;21(1):64-9. doi: 10.1177/1074248415581176. Epub 2015 Apr 21.

DOI:10.1177/1074248415581176
PMID:25901009
Abstract

BACKGROUND

Intestinal barrier dysfunction would lead to a rigorous inflammatory reaction due to the translocation of intestinal lumen-derived bacteria and endotoxins. The aim of the present study was to investigate whether intestinal barrier dysfunction occurs in patients with acute Stanford type A aortic dissection (ATAAD) and to determine its potential relationship with the plasma levels of several inflammatory biomarkers in the progression of ATAAD.

DESIGN AND METHODS

Serum samples from a total of 46 patients with ATAAD and 36 healthy volunteers were prospectively collected and analyzed. The serum levels of diamine oxidase (DAO), lactate dehydrogenase (LDH), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and C-reactive protein (CRP) were measured using colorimetric assay, enzyme-linked immunosorbent assay, and immunoturbidimetric assay.

RESULTS

Serum levels of DAO, LDH, IL-6, TNF-α, and CRP in patients with ATAAD were significantly higher than those in healthy participants. A significantly positive correlation between DAO activity and IL-6 (r = .56, P < .001), TNF-α (r = .63, P < .001), and CRP (r = .53, P < .001) was observed. Moreover, the activity of DAO correlated negatively with the Pao 2/fraction of inspired oxygen (Fio 2) ratio (r = -.39, P = .007).

CONCLUSIONS

Intestinal barrier dysfunction, reflected by an increased level of serum DAO, may play an important role in the development of systemic inflammatory responses in patients with ATAAD. Therefore, strategies of preserving a normal intestinal barrier function may open new horizons in the treatment of inflammation-related adverse events in the setting of ATAAD.

摘要

背景

由于肠腔内细菌和内毒素的易位,肠道屏障功能障碍会导致严重的炎症反应。本研究旨在调查急性A型主动脉夹层(ATAAD)患者是否发生肠道屏障功能障碍,并确定其与ATAAD进展过程中几种炎症生物标志物血浆水平的潜在关系。

设计与方法

前瞻性收集并分析了46例ATAAD患者和36名健康志愿者的血清样本。采用比色法、酶联免疫吸附测定法和免疫比浊法测定血清中二胺氧化酶(DAO)、乳酸脱氢酶(LDH)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)和C反应蛋白(CRP)的水平。

结果

ATAAD患者的血清DAO、LDH、IL-6、TNF-α和CRP水平显著高于健康参与者。观察到DAO活性与IL-6(r = 0.56,P < 0.001)、TNF-α(r = 0.63,P < 0.001)和CRP(r = 0.53,P < 0.001)之间存在显著正相关。此外,DAO活性与动脉血氧分压/吸入氧分数(Pao₂/Fio₂)比值呈负相关(r = -0.39,P = 0.007)。

结论

血清DAO水平升高反映的肠道屏障功能障碍可能在ATAAD患者全身炎症反应的发展中起重要作用。因此,维持正常肠道屏障功能的策略可能为ATAAD相关炎症不良事件的治疗开辟新的前景。

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