Wang Xunjiang, Zhang Wei, Yang Yongfeng, Chen Yiran, Zhuge Yuzheng, Xiong Aizhen, Yang Li, Wang Zhengtao
The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai, China.
Front Pharmacol. 2021 Feb 19;12:627126. doi: 10.3389/fphar.2021.627126. eCollection 2021.
The -induced hepatic sinusoidal obstruction syndrome (HSOS) is closely related to pyrrolizidine alkaloids (PAs), and its prevalence has been increasing worldwide in recent years. However, no effective therapy for PA-induced HSOS in clinics is available, partially due to the failure of quick diagnosis. This study aims to identify blood microRNA (miRNA) signatures as potential biomarkers for PA-induced HSOS in clinics. The microarray-based miRNA profiling was performed on blood samples of the discovery cohort, which consisted of nine patients with HSOS and nine healthy donors. Differentially expressed miRNAs were further confirmed using a validation cohort, which consisted of 20 independent patients with HSOS. In addition, the rat model was established through the oral administration of the total alkaloid extract from to investigate the association of miRNA biomarkers with the progression of HSOS. Bioinformatic analyses, including GO and KEGG enrichment, receiver operating characteristics curve, and correlation analyses were conducted to evaluate the accuracy of the potential miRNA biomarkers. Three miRNAs, namely miR-148a-3p, miR-362-5p, and miR-194-5p, were overexpressed in patients and rats with PA-induced HSOS. These miRNAs were positively related to the severity of liver injury and displayed considerable diagnostic accuracy for patients with HSOS with areas under the curve over 0.87. In summary, this study demonstrated that three miRNAs, hsa-miR-148a-3p, hsa-miR-362-5p, and hsa-miR-194-5p, might serve as potential biomarkers for PA-induced HSOS in clinics.
[某种物质]诱导的肝窦阻塞综合征（HSOS）与吡咯里西啶生物碱（PAs）密切相关，近年来其在全球的患病率呈上升趋势。然而，临床上尚无针对PA诱导的HSOS的有效治疗方法，部分原因是难以快速诊断。本研究旨在鉴定血液微小RNA（miRNA）特征作为临床上PA诱导的HSOS的潜在生物标志物。对发现队列的血液样本进行基于微阵列的miRNA谱分析，该队列由9例HSOS患者和9名健康供体组成。使用由20例独立的HSOS患者组成的验证队列进一步确认差异表达的miRNA。此外，通过口服[某种植物]的总生物碱提取物建立大鼠模型，以研究miRNA生物标志物与HSOS进展的关联。进行了包括GO和KEGG富集、受试者工作特征曲线及相关性分析在内的生物信息学分析，以评估潜在miRNA生物标志物的准确性。三种miRNA，即miR-148a-3p、miR-362-5p和miR-194-5p，在PA诱导的HSOS患者和大鼠中过表达。这些miRNA与肝损伤严重程度呈正相关，对HSOS患者显示出相当高的诊断准确性，曲线下面积超过0.87。总之，本研究表明三种miRNA，即hsa-miR-148a-3p、hsa-miR-362-5p和hsa-miR-194-5p，可能作为临床上PA诱导的HSOS的潜在生物标志物。
