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微透析导管取样的炎症标志物可区分肝移植物中的排斥反应和缺血。

Inflammatory markers sampled by microdialysis catheters distinguish rejection from ischemia in liver grafts.

机构信息

Division of Emergencies and Critical Care, Oslo University Hospital-Rikshospitalet, Oslo, Norway.

出版信息

Liver Transpl. 2012 Dec;18(12):1421-9. doi: 10.1002/lt.23503. Epub 2012 Sep 26.

Abstract

Rejection and ischemia are serious complications after liver transplantation. Early detection is mandatory, but specific markers are largely missing, particularly for rejection. The objective of this study was to explore the ability of microdialysis catheters inserted in liver grafts to detect and discriminate rejection and ischemia through postoperative measurements of inflammatory mediators. Microdialysis catheters with a 100-kDa pore size were inserted into 73 transplants after reperfusion. After the study's completion, complement activation product 5a (C5a), C-X-C motif chemokine 8 (CXCL8), CXCL10, interleukin-1 (IL-1) receptor antagonist, IL-6, IL-10, and macrophage inflammatory protein 1β were analyzed en bloc in all grafts with biopsy-confirmed rejection (n = 12), in grafts with vascular occlusion/ischemia (n = 4), and in reference grafts with a normal postoperative course of circulating transaminase and bilirubin levels (n = 17). The inflammatory mediators were elevated immediately after graft reperfusion and decreased toward low, stable values during the first 24 hours in nonischemic grafts. In grafts suffering from rejection, CXCL10 increased significantly (P = 0.008 versus the reference group and P = 0.002 versus the ischemia group) 2 to 5 days before increases in circulating alanine aminotransferase and bilirubin levels. The area under the receiver operating characteristic curve was 0.81. Grafts with ischemia displayed increased levels of C5a (P = 0.002 versus the reference group and P = 0.008 versus the rejection group). The area under the curve was 0.99. IL-6 and CXCL8 increased with both ischemia and rejection. In conclusion, CXCL10 and C5a were found to be selective markers for rejection and ischemia, respectively.

摘要

排斥反应和缺血是肝移植后的严重并发症。早期发现是强制性的,但缺乏特定的标志物,特别是对于排斥反应。本研究的目的是通过术后炎症介质的测量,探讨插入肝移植物中的微透析导管检测和区分排斥反应和缺血的能力。在再灌注后,将 100 kDa 孔径的微透析导管插入 73 个移植中。在研究完成后,用活检证实的排斥反应(n = 12)、血管阻塞/缺血(n = 4)和参考移植(n = 17)的所有移植物中分析补体激活产物 5a(C5a)、C-X-C 基序趋化因子 8(CXCL8)、CXCL10、白细胞介素-1(IL-1)受体拮抗剂、IL-6、IL-10 和巨噬细胞炎症蛋白 1β。在非缺血移植中,炎症介质在再灌注后立即升高,并在第 1 天内降低到低而稳定的值。在发生排斥反应的移植中,CXCL10 在循环丙氨酸氨基转移酶和胆红素水平升高前 2 至 5 天显著升高(与参考组相比,P = 0.008,与缺血组相比,P = 0.002)。受体操作特征曲线下面积为 0.81。发生缺血的移植显示 C5a 水平升高(与参考组相比,P = 0.002,与排斥组相比,P = 0.008)。曲线下面积为 0.99。IL-6 和 CXCL8 随着缺血和排斥反应而增加。总之,发现 CXCL10 和 C5a 分别是排斥反应和缺血的选择性标志物。

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