HMGB1与RAGE水平在急性主动脉夹层肺损伤患者中的变化及临床意义

Changes in HMGB1 and RAGE levels in patients with lung injury induced by acute aortic dissection and the clinical significance

摘要:

目的：探讨急性主动脉夹层（AAD）患者血清高迁移率族蛋白B1（HMGB1）与晚期糖基化终产物受体（RAGE）水平与继发急性肺损伤的关系。
方法：选取2016年3月—2018年5月经全主动脉CTA以及超声心动图等影像学检查明确诊断的AAD患者56例为研究对象。按静态吸氧状态下氧合指数（PaO2/FiO2）大小将患者分为肺损伤组（21例）与非肺损伤组（35例）。随机选取健康体检人员30例为对照组。AAD患者入院后每4 小时抽血次，对照组受试者仅抽取1次清晨空腹肘静脉血。采用ELISA法检测血清HMGB1、RAGE水平，同时检测PaO2、计算PaO2/FiO2。
结果：与健康对照组比较，两组AAD患者入院后24 h的HMGB1、RAGE水平均明显高于健康对照组，且两者在肺损伤组均明显高于非肺损伤组（均P<0.05）。两组AAD患者入院后HMGB1、RAGE水平不断上升，而PaO2/FiO2逐渐降低，并均入院后48~60 h达到峰值，肺损伤组的3项指标的变化幅度均明显大于非肺损伤组（均P<0.05）；随着发病时间的推移，HMGB1、RAGE水平达到峰值后下降，PaO2/FiO2逐渐回升。AAD患者中，HMGB1与RAGE水平与PaO2/FiO2均呈明显负相关（r=-0.940、
-0.794）。
结论：HMGB1/RAGE信号通路可能在AAD肺损伤中发挥着重要的作用，随着HMGB1、RAGE水平的升高，肺损伤程度逐渐加重，监测HMGB1、RAGE水平可以对AAD并发肺损伤的风险进行评估；对HMGB1/RAGE信号通路深入研究可能会为AAD肺损伤的干预提供靶点。

Abstract:

Objective: To investigate the association of the serum levels of high mobility group protein B1 (HMGB1) and advanced glycosylation end-product receptor (RAGE) in patients with acute lung injury secondary to acute aortic dissection (AAD).
Methods: From March 2016 to May 2018, 56 consecutive patients with AAD who were diagnosed by CTA of the whole aorta and echocardiography were enrolled. According to the values of oxygenation index (PaO2/FiO2) during oxygen inhalation in a resting state, the patients were divided into lung injury group (21 cases) and non-lung injury group (35 cases), and 30 individuals undergoing health maintenance examination were randomly selected as control group. Blood samples were drawn once per 4 h in the AAD patients after admission, and in the control group, fasting blood samples were taken only once from the elbow vein in the morning. The serum levels of HMGB1 and RAGE were measured by ELISA and PaO2 values were detected for calculating PaO2/FiO2.
Results: In both groups of AAD patients, the serum levels of HMGB1 and RAGE at 24 h after admission were significantly higher than those in the healthy control group, and which were also significantly higher in lung injury group than those in non-lung injury group (all P<0.05). In both groups of AAD patients, the serum levels of HMGB1 and RAGE were continuously increased, while the PaO2/FiO2 values were gradually decreased, and all reached a peak value within 48-60 h after admission. The changing amplitudes of the 3 variables were all significantly greater in lung injury group than those in non-lung injury group (all P<0.05). After they reached the peak values, the HMGB1 and RAGE levels gradually decreased, while the PaO2/FiO2 values correspondingly increased as time elapsed. In AAD patients, both HMGB1 and RAGE levels presented a significantly negative correlation with PaO2/FiO2 value (r=–0.940, –0.794).
Conclusion: The HMGB1/RAGE signaling pathway may play an important role in the occurrence of lung injury in AAD, and lung injury may be worsened with the increase of HMGB1 and RAGE levels. Monitoring of the HMGB1 and RAGE levels can help to evaluate the risk of lung injury after AAD. Further investigations of the HMGB1/RAGE signaling pathway may provide interventional targets for lung injury after AAD.