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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Quantitative analyses and transcriptomic profiling of circulating messenger RNAs as biomarkers of rat liver injury.
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Quantitative analyses and transcriptomic profiling of circulating messenger RNAs as biomarkers of rat liver injury.

机译：循环信使RNA的定量分析和转录组谱分析是大鼠肝损伤的生物标志物。

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摘要

Serum aminotransferases have been the clinical standard for evaluating liver injury for the past 50-60 years. These tissue enzymes lack specificity, also tracking injury to other tissues. New technologies assessing tissue-specific messenger RNA (mRNA) release into blood should provide greater specificity and permit indirect assessment of gene expression status of injured tissue. To evaluate the potential of circulating mRNAs as biomarkers of liver injury, rats were treated either with hepatotoxic doses of D-(+)-galactosamine (DGAL) or acetaminophen (APAP) or a myotoxic dose of bupivacaine HCl (BPVC). Plasma, serum, and liver samples were obtained from each rat. Serum alanine aminotransferase and aspartate aminotransferase were increased by all three compounds, whereas circulating liver-specific mRNAs were only increased by the hepatotoxicants. With APAP, liver-specific mRNAs were significantly increased in plasma at doses that had no effect on serum aminotransferases or liver histopathology. Characterization of the circulating mRNAs by sucrose density gradient centrifugation revealed that the liver-specific mRNAs were associated with both necrotic debris and microvesicles. DGAL treatment also induced a shift in the size of plasma microvesicles, consistent with active release of microvesicles following liver injury. Finally, gene expression microarray analysis of the plasma following DGAL and APAP treatment revealed chemical-specific profiles. CONCLUSION: The comparative analysis of circulating liver mRNAs with traditional serum transaminases and histopathology indicated that the circulating liver mRNAs were more specific and more sensitive biomarkers of liver injury. Further, the possibility of identifying chemical-specific transcriptional profiles from circulating mRNAs could open a range of possibilities for identifying the etiology of drug/chemical-induced liver injury.
机译：在过去的50-60年中，血清氨基转移酶一直是评估肝损伤的临床标准。这些组织酶缺乏特异性，还跟踪对其他组织的损伤。评估组织特异性信使RNA（mRNA）释放到血液中的新技术应提供更高的特异性，并可以间接评估受损组织的基因表达状态。为了评估循环mRNA作为肝损伤生物标志物的潜力，用肝毒性剂量的D-（+）-半乳糖胺（DGAL）或对乙酰氨基酚（APAP）或肌毒性剂量的布比卡因HCl（BPVC）治疗大鼠。从每只大鼠获得血浆，血清和肝样品。三种化合物均增加了血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶的含量，而循环肝特异性mRNA仅因肝毒性剂而增加。使用APAP，在不影响血清氨基转移酶或肝组织病理学的剂量下，血浆中的肝特异性mRNA显着增加。蔗糖密度梯度离心法对循环中的mRNA的表征表明，肝脏特异性mRNA与坏死碎片和微囊泡均相关。 DGAL治疗还引起血浆微泡大小的改变，这与肝损伤后主动释放微泡相一致。最后，DGAL和APAP处理后血浆的基因表达微阵列分析揭示了化学特异谱。结论：将循环肝mRNA与传统血清转氨酶及组织病理学进行比较分析表明，循环肝mRNA是肝损伤的更特异性和更敏感的生物标志物。此外，从循环的mRNA中鉴定化学特异的转录谱的可能性可以为鉴定药物/化学性肝损伤的病因学提供一系列可能性。

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