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肝缺血再灌注损伤中miR-370表达的改变与核因子κB(NF-κB)相关因子水平相关。

Altered miR-370 expression in hepatic ischemia-reperfusion injury correlates with the level of nuclear kappa B (NF-κB) related factors.

作者信息

Zhu Jie, Zhu Fangfang, Song Wenfeng, Zhang Bin, Zhang Xie, Jin Xiaofeng, Li Hong

机构信息

College of Medicine, Ningbo University, China.

Ningbo Medical Centre of LIHuiLi Hospital, China.

出版信息

Gene. 2017 Apr 5;607:23-30. doi: 10.1016/j.gene.2016.12.026. Epub 2016 Dec 30.

DOI:10.1016/j.gene.2016.12.026
PMID:28043920
Abstract

BACKGROUND & AIMS: MicroRNAs (miRNAs) are a class of small endogenous, non-coding RNAs that regulate gene expression at both the transcription and translation levels. Whether miRNAs have taken part in liver ischemia-reperfusion (IR) injury was rarely reported. The purpose of this article is to investigate the potential role of miR-370 in hepatic IR injury.

METHODS

Male C57BL/6 mice were divided into 5 groups (sham-operated group, I/R group, IPC group, antagomir-370 group and antagomir-NC), and the expression levels of miR-370 were assessed by quantitative real-time PCR. Serum enzyme analysis and histological examination of liver were used as the index of the effect of miR-370 on hepatic IR injury and following treatment of mice with antagomir-370 or antagomir-NC. The classical pathway factors of NF-κB (TAK, TAB, TAB, IkBα, IKKα, IKKβ, p50, p65) were studied by quantitative real-time PCR and Western blot.

RESULTS

The results showed that the IR group's miR-370 expression level was significantly upregulated as compared with the sham-operated group and IPC group. Also inhibition of miR-370 led to the low expression levels of miR-370 and low levels of serum aminotransferase and hepatic histological damage as compared with the IR group. Quantitative real-time PCR showed the levels of TAK1, TAB, TAB2, IkBα, IKKα, p65 was elevated when improving the miR-370 levels, at the same time, Western blot showed the levels of TAK, TAB, TAB, IkBα, IKKα, IKKβ, p50, p65 were all elevated.

CONCLUSION

miR-370 acting via NF-κB might play a crucial role in hepatic IR injury, and inhibition of miR-370 could alleviate the injury to the liver. And miR-370 might positively regulated the NF-κB pathway.

摘要

背景与目的

微小RNA(miRNA)是一类内源性小非编码RNA,可在转录和翻译水平调节基因表达。miRNA是否参与肝缺血再灌注(IR)损伤鲜有报道。本文旨在研究miR-370在肝脏IR损伤中的潜在作用。

方法

将雄性C57BL/6小鼠分为5组(假手术组、I/R组、缺血预处理组、抗miR-370组和抗miR-NC组),通过定量实时PCR评估miR-370的表达水平。以血清酶分析和肝脏组织学检查作为miR-370对肝脏IR损伤影响及抗miR-370或抗miR-NC处理小鼠后的效果指标。通过定量实时PCR和蛋白质印迹法研究NF-κB的经典途径因子(TAK、TAB、TAB、IkBα、IKKα、IKKβ、p50、p65)。

结果

结果显示,与假手术组和缺血预处理组相比,I/R组的miR-370表达水平显著上调。此外,与I/R组相比,抑制miR-370导致miR-370表达水平降低以及血清转氨酶水平降低和肝脏组织学损伤减轻。定量实时PCR显示,提高miR-370水平时,TAK1、TAB、TAB2、IkBα、IKKα、p65的水平升高,同时蛋白质印迹显示TAK、TAB、TAB、IkBα、IKKα、IKKβ、p50、p65的水平均升高。

结论

miR-370通过NF-κB发挥作用可能在肝脏IR损伤中起关键作用,抑制miR-370可减轻肝脏损伤。并且miR-370可能正向调节NF-κB途径。

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