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首页> 外文期刊>Archives of Toxicology >Comprehensive analysis of serum microRNAs in hepatic sinusoidal obstruction syndrome (SOS) in rats: implication as early phase biomarkers for SOS
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Comprehensive analysis of serum microRNAs in hepatic sinusoidal obstruction syndrome (SOS) in rats: implication as early phase biomarkers for SOS

机译：大鼠肝正弦梗阻综合征（SOS）中血清MicroRNA的综合分析：含义作为SOS的早期生物标志物

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Sinusoidal obstruction syndrome (SOS) is a liver injury caused by clinical chemotherapy, of which pathogenesis is associated with the damage in liver sinusoidal endothelial cells (LSEC). The unavailability of appropriate specific biomarkers for the early diagnosis of SOS may potentially overlook SOS patients. In this study, we sought to find serum microRNAs (miRNAs) as non-invasive biomarkers for investigating SOS in rats. Male Sprague–Dawley rats were orally administered monocrotaline, and then, their livers and sera were collected after 0.25, 0.5, 1, 2, 4, and 7?days. The rats showed a typical SOS phenotype including LSEC damage as early as day 0.25, followed by severe hepatocyte damage on day 2, and developed hepatic fibrosis from days 4 to 7. The miRNA microarray showed that 65 serum miRNAs were increased in their levels on day 0.25, when LSEC damage was observed, while hepatocyte damage was absent. Among the increased serum miRNAs on days 0.25–1, miR-511-3p was enriched in normal LSECs and miR-21-5p was in both LSECs and hepatocytes, suggesting that they were released into blood from the damaged LSECs. The miR-122-5p, miR-192-5p, and miR-101b-3p, which were enriched in hepatocytes, reached the highest levels in serum on day 2, suggesting their utility as indicators for hepatocyte damage. No miRNA showing an increasing trend from days 4 to 7 was found as a biomarker for fibrosis. In conclusion, we found that LSEC-derived miR-21-5p and especially miR-511-3p in serum would serve as early phase biomarkers for SOS in response to LSEC damage.
机译：正弦梗阻综合征（SOS）是由临床化疗引起的肝损伤，其中发病机制与肝窦内皮细胞（LSEC）的损伤有关。适当的特异性生物标志物用于早期诊断SOS可能会忽略SOS患者。在这项研究中，我们试图寻找血清MicroRNA（miRNA）作为用于研究大鼠SOS的非侵入性生物标志物。男性Sprague-Dawley大鼠口服占龙甲醛，然后，0.25,0.5,1,2,4和7.天后收集它们的肝脏和血清。大鼠表现出典型的SOS表型，包括LSEC损伤，早在0.25天，然后在第2天进行严重的肝细胞损伤，并在4至7天开发肝纤维化。MiRNA微阵列显示65天的MiRNA在其水平上增加了65个血清miRNA 0.25，当观察到LSEC损伤时，而肝细胞损伤不存在。在0.25-1天的血清miRNA增加中，MiR-511-3P在正常LSECS中富集，MiR-21-5P在LSEC和肝细胞中，表明它们被释放到血液中损坏的LSEC。 MiR-122-5P，MiR-192-5P和MiR-101B-3P，富集在肝细胞中，第2天达到了血清中的最高水平，表明它们作为肝细胞损伤的指标的实用性。没有发现从40至7天开始增加趋势的miRNA作为纤维化的生物标志物。总之，我们发现LSEC衍生的miR-21-5p，特别是miR-511-3p在血清中作为SOS的早期生物标志物，响应于LSEC损伤。

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