Application of iTRAQ-Based Quantitative Proteomics Approach to Identify Deregulated Proteins Associated with Liver Toxicity Induced by Polygonum Multiflorum in Rats
Application of iTRAQ-Based Quantitative Proteomics Approach to Identify Deregulated Proteins Associated with Liver Toxicity Induced by Polygonum Multiflorum in Rats
复制标题
应用基于 iTRAQ 的定量蛋白质组学方法鉴定与何首乌诱导的大鼠肝脏毒性相关的失调蛋白质
DOI：
10.1159/000484229
复制
发表时间：
2017-01-01
影响因子：
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通讯作者：
Ni, Jian
中科院分区：
文献类型：
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作者：
Lin, Longfei;Li, Hui;Ni, Jian
背景/目的：何首乌及其制剂引起的不良反应，尤其是肝损伤的临床报道近年来受到广泛关注。本研究旨在通过iTRAQ定量蛋白质组学研究不同PM提取物对小鼠肝脏的毒性作用机制。方法：给大鼠灌胃给予不同PM提取物90d，通过生化指标、氧化损伤指标和苏木精-伊红(HE)染色评价其肝毒性作用。然后，用iTRAQ定量蛋白质组学方法对其肝毒性机制进行了研究。结果：生化和组织病理学分析结果表明，不同剂量的PM提取物对大鼠均有肝损伤作用，证明PM提取物均有肝毒性作用。从生化指标的结果来看，总提物组和其他组的肝毒性机制可能不同。ITRAQ蛋白质组学研究表明，PM引起的肝毒性主要与线粒体功能相关的氧化磷酸化途径活性异常有关。结论：iTRAQ蛋白质组学研究表明PM的肝毒性主要与氧化磷酸化途径有关。NADH脱氢酶家族蛋白和SLc16a2可能是PM肝毒性的潜在生物标志物(C)2017年作者(S)由S.Karger AG，巴塞尔出版
Background/Aims: Clinical reports on adverse reactions that result from Polygonum multiflorum (PM) and its preparations, especially regarding liver injury, have recently received widespread attention. This study aimed to investigate the mechanism of hepatotoxicity induced by different PM extracts through iTRAQ quantitative proteomics. Methods: The different PM extracts were orally administrated for 90 days to rats, and the hepatotoxicity effect was evaluated through measurement of biochemical indexes, oxidative damage indexes and hematoxylin-eosin (HE) staining. Then, the hepatotoxicity mechanism was investigated by iTRAQ quantitative proteomics. Results: The results of biochemical and histopathological analyses showed that liver injury occurred in all groups of rats given by various PM extracts, which proved all of the PM extracts could induce hepatotoxicity. The hepatotoxicity mechanism may differ between the total extract group and the other groups through the results of biochemical indicators. The iTRAQ proteomics study showed that hepatotoxicity resulting from PM was mainly related to the abnormal activity of mitochondrion function-related oxidative phosphorylation pathways. Conclusion: This iTRAQ proteomics study revealed that the hepatotoxicity induced by PM is primarily related to the oxidative phosphorylation pathways. NADH dehydrogenase family proteins and Slc16a2 could be potential biomarkers of hepatotoxicity resulting from PM. (c) 2017 The Author(s) Published by S. Karger AG, Basel