Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Organ Transplantation Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Int Immunopharmacol. 2017 Oct;51:140-147. doi: 10.1016/j.intimp.2017.08.008. Epub 2017 Aug 30.
Inflammatory responses play an important role in the tissue injury during liver ischemia/reperfusion (I/R). We previously reported that resolvin D1 (RvD1) administrated prior to hepatic I/R attenuates liver injury through inhibition of inflammatory response. In this study, we investigated the effects of the aspirin-triggered resolvin D1 (AT-RvD1) on hepatic I/R and the role of miR-146b in this process.
Partial warm ischemia was performed in the left and middle hepatic lobes of Sprague-Dawley rats for 1h, followed by 6h of reperfusion. Rats received either AT-RvD1 (5μg/kg), vehicle, or AT-RvD1+miR-146b antagomir by intravenous injection 30min before ischemia. Blood and tissue samples of the rats were collected after 6-h reperfusion.
Pretreatment with AT-RvD1 significantly diminished I/R-induced elevations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and significantly blunted the histological injury of the liver. Moreover, AT-RvD1 significantly inhibited inflammatory response, as indicated by attenuations of TNF-α and myeloperoxidase levels. Reduced apoptosis, and increased survival rate were observed in the AT-RvD1 group compared with the control I/R group. AT-RvD1 pretreatment increased miR-146b expression in the liver of the rats with hepatic I/R. Administration of miR-146b antagomir impaired the effects of AT-RvD1 on hepatic I/R injury in rats. Downregulation of miR-146b inhibited TRAF6 and NF-κB expression in liver.
Pre-administration of AT-RvD1 attenuates hepatic I/R injury partly through modulation of miR-146b.
在肝脏缺血/再灌注（I/R）过程中，炎症反应起着重要作用。我们之前的研究表明，在肝 I/R 前给予 resolvin D1（RvD1）可通过抑制炎症反应来减轻肝损伤。在这项研究中，我们研究了阿司匹林触发的 resolvin D1（AT-RvD1）对肝 I/R 的影响，以及在此过程中 miR-146b 的作用。
对 Sprague-Dawley 大鼠的左、中肝叶进行部分热缺血 1 小时，然后再灌注 6 小时。大鼠在缺血前 30 分钟分别静脉注射 AT-RvD1（5μg/kg）、载体或 AT-RvD1+miR-146b 拮抗剂。再灌注 6 小时后采集大鼠的血液和组织样本。
AT-RvD1 预处理显著降低了 I/R 诱导的丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）升高，并显著减轻了肝脏的组织损伤。此外，AT-RvD1 显著抑制了炎症反应，表现为 TNF-α和髓过氧化物酶水平的降低。与对照组相比，AT-RvD1 组的细胞凋亡减少，存活率提高。与 I/R 组相比，AT-RvD1 预处理组大鼠肝脏中 miR-146b 的表达增加。给予 miR-146b 拮抗剂可损害 AT-RvD1 对大鼠肝 I/R 损伤的作用。下调 miR-146b 可抑制 TRAF6 和 NF-κB 在肝脏中的表达。
AT-RvD1 的预先给药部分通过调节 miR-146b 来减轻肝 I/R 损伤。
