Chen Q, Kong L, Xu X, Geng Q, Tang W, Jiang W
Department of Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Transplant Proc. 2013 Mar;45(2):492-6. doi: 10.1016/j.transproceed.2012.10.045.
MicroRNAs (miRNAs), 21-23-nucleotide noncoding RNAs, act as regulators of gene expression transcriptionally. MicroRNA-146a(miR-146a) has been demonstrated to be one of the key molecules in oncogenesis and inflammatory responses. Few data describe the expression of miR-146a in liver ischemia-reperfusion (IR) injury. The present study sought to explore the relationship of miR-146a to Toll-like receptor 4 (TLR4) signaling pathways in a rat model of warm IR injury.
The expression of miR-146a was detected by real-time reverse-transcriptase polymerase chain reaction using a partial warm hepatic IR injury model. The expression of TLR4, tumor necrosis factor receptor-associated factor 6 (TRAF6), and interleukin-1 receptor-associated kinase (IRAK 1) protein was assessed by Western blotting as well as the signaling pathways induced by TLR4.
The expression of hepatic miR-146a was down-regulated in IR injury during the 24 hours after reperfusion, reaching the lowest level at 6 hours after reperfusion. Increases in TLR4, TRAF6, and IRAK1 were accompanied by decreased miR-146a during the 24 hours after reperfusion, peaking at 6 hours. Immunohistochemistry showed cytoplasmic expression of cells positive for TLR4, and nuclear expression of cells positive for nuclear factor κB p65 and c-jun to be increased among IR groups after reperfusion.
miR-146a was down-regulated in the early stage of liver IR injury.
微小RNA（miRNA）是一类长度为21 - 23个核苷酸的非编码RNA，在转录水平发挥基因表达调控作用。微小RNA - 146a（miR - 146a）已被证明是肿瘤发生和炎症反应中的关键分子之一。关于miR - 146a在肝脏缺血再灌注（IR）损伤中的表达情况，相关数据较少。本研究旨在探讨在大鼠温缺血再灌注损伤模型中miR - 146a与Toll样受体4（TLR4）信号通路之间的关系。
采用部分肝脏温缺血再灌注损伤模型，通过实时逆转录聚合酶链反应检测miR - 146a的表达。采用蛋白质免疫印迹法评估TLR4、肿瘤坏死因子受体相关因子6（TRAF6）和白细胞介素 - 1受体相关激酶（IRAK 1）蛋白的表达以及TLR4诱导的信号通路。
再灌注后24小时内，肝脏miR - 146a的表达在IR损伤中下调，在再灌注后6小时达到最低水平。再灌注后24小时内，TLR4、TRAF6和IRAK1的增加伴随着miR - 146a的减少，在6小时达到峰值。免疫组织化学显示，再灌注后IR组中TLR4阳性细胞的细胞质表达以及核因子κB p65和c - jun阳性细胞的核表达增加。
miR - 146a在肝脏IR损伤早期下调。
