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肝脏特异性 microRNAs 作为纳米材料诱导肝损伤的生物标志物。

Liver-specific microRNAs as biomarkers of nanomaterial-induced liver damage.

机构信息

Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.

出版信息

Nanotechnology. 2013 Oct 11;24(40):405102. doi: 10.1088/0957-4484/24/40/405102. Epub 2013 Sep 12.

Abstract

Although nanomaterials are being used in various fields, their safety is not yet sufficiently understood. We have been attempting to establish a nanomaterials safety-assessment system by using biomarkers to predict nanomaterial-induced adverse biological effects. Here, we focused on microRNAs (miRNAs) because of their tissue-specific expression and high degree of stability in the blood. We previously showed that high intravenous doses of silica nanoparticles of 70 nm diameter (nSP70) induced liver damage in mice. In this study, we compared the effectiveness of serum levels of liver-specific or -enriched miRNAs (miR-122, miR-192, and miR-194) with that of conventional hepatic biomarkers (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) as biomarkers for nSP70. After mice had been treated with nSP70, their serum miRNAs levels were measured by using quantitative RT-PCR. Serum levels of miR-122 in nSP70-treated mice were the highest among the three miRNAs. The sensitivity of miR-122 for liver damage was at least as good as those of ALT and AST. Like ALT and AST, miR-122 may be a useful biomarker of nSP70. We believe that these findings will help in the establishment of a nanomaterials safety-assessment system.

摘要

尽管纳米材料被广泛应用于各个领域,但它们的安全性尚未得到充分的了解。我们一直在尝试利用生物标志物来预测纳米材料诱导的不良生物学效应,从而建立纳米材料安全性评估体系。在这里,我们专注于 microRNAs(miRNAs),因为它们在组织中具有特异性表达,并且在血液中具有高度稳定性。我们之前曾表明,高剂量静脉注射 70nm 直径的二氧化硅纳米颗粒(nSP70)会导致小鼠肝脏损伤。在这项研究中,我们比较了血清中肝脏特异性或富集的 miRNAs(miR-122、miR-192 和 miR-194)与传统肝脏生物标志物(丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST))作为 nSP70 生物标志物的效果。在给小鼠用 nSP70 处理后,我们使用定量 RT-PCR 测量了它们血清中 miRNAs 的水平。在 nSP70 处理的小鼠中,miR-122 的血清水平在这三种 miRNAs 中是最高的。miR-122 对肝损伤的敏感性至少与 ALT 和 AST 一样好。与 ALT 和 AST 一样,miR-122 可能是 nSP70 的有用生物标志物。我们相信这些发现将有助于建立纳米材料安全性评估体系。

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