Department of Surgery and Laboratory of Experimental Transplantation and Intestinal Surgery, Erasmus MC: University Medical Center Rotterdam, Rotterdam, the Netherlands.
Liver Transpl. 2012 Mar;18(3):290-7. doi: 10.1002/lt.22438.
Recent animal and human studies have highlighted the potential of hepatocyte-derived microRNAs (HDmiRs) in serum as early, stable, sensitive, and specific biomarkers of liver injury. Their usefulness in human liver transplantation, however, has not been addressed. The aim of this study was to investigate serum HDmiRs as markers of hepatic injury and rejection in liver transplantation. Serum samples from healthy controls and liver transplant recipients (n = 107) and peritransplant liver allograft biopsy samples (n = 45) were analyzed via the real-time polymerase chain reaction quantification of HDmiRs (miR-122, miR-148a, and miR-194). The expression of miR-122 and miR-148a in liver tissue was significantly reduced with prolonged graft warm ischemia times. Conversely, the serum levels of these HDmiRs were elevated in patients with liver injury and positively correlated with aminotransferase levels. HDmiRs appear to be very sensitive because patients with normal aminotransferase values (<50 IU/L) had 6- to 17-fold higher HDmiR levels in comparison with healthy controls (P < 0.005). During an episode of acute rejection, serum HDmiRs were elevated up to 20-fold, and their levels appeared to rise earlier than aminotransferase levels. HDmiRs in serum were stable during repeated freezing and thawing. In conclusion, this study shows that liver injury is associated with the release of HDmiRs into the circulation. HDmiRs are promising candidates as early, stable, and sensitive biomarkers of rejection and hepatic injury after liver transplantation.
最近的动物和人类研究强调了肝细胞衍生的 microRNAs（HDmiRs）在血清中作为肝损伤的早期、稳定、敏感和特异性生物标志物的潜力。然而，它们在人类肝移植中的应用尚未得到解决。本研究旨在探讨血清 HDmiRs 作为肝移植中肝损伤和排斥反应的标志物。通过实时聚合酶链反应定量分析 HDmiRs（miR-122、miR-148a 和 miR-194），分析了来自健康对照者和肝移植受者（n = 107）的血清样本和移植前肝移植肝活检样本（n = 45）。miR-122 和 miR-148a 在肝组织中的表达随着移植物热缺血时间的延长而显著降低。相反，这些 HDmiRs 的血清水平在肝损伤患者中升高，并与转氨酶水平呈正相关。HDmiRs 似乎非常敏感，因为转氨酶值正常（<50IU/L）的患者与健康对照者相比，HDmiR 水平高出 6-17 倍（P < 0.005）。在急性排斥反应发作期间，血清 HDmiRs 升高了 20 倍，其水平似乎比转氨酶水平更早升高。血清 HDmiRs 在反复冷冻和解冻过程中稳定。总之，本研究表明肝损伤与 HDmiRs 释放到循环中有关。HDmiRs 作为肝移植后排斥反应和肝损伤的早期、稳定和敏感的生物标志物具有很大的应用前景。
