Chungen Yan, Dongfang Zhu, Guoyuan Xia
Department of Gastroenterology, Affiliated Hospital of Shaoxing University, Zhejiang, China.
Department of Lab Medicine, Affiliated Hospital of Shaoxing University, Zhejiang, China.
Transplant Proc. 2020 Apr;52(3):1007-1013. doi: 10.1016/j.transproceed.2020.01.046. Epub 2020 Mar 4.
Hepatic ischemia/reperfusion injury (IRI) is a severe and common clinical challenge involved in liver surgery and transplantation. MicroRNA-146a (miR-146a) has recently been reported to be abnormally expressed in hepatic IRI, but the underlying mechanism is not fully elucidated. Accumulating evidences showed miR-146a targets Toll-like receptor 4 (TLR4) signaling pathway. Here, we found that miR-146a inhibited TLR4 signaling pathway accompanied by attenuated liver dysfunction, histologic injury and inflammation. Conversely, miR-146a inhibition increased TLR4 and interleukin-1 receptor-associated kinase, accompanied by exacerbated hepatic IRI and inflammation. Taken together, these data indicated that miR-146a protect against hepatic IRI via inhibiting TLR4 signaling pathway. In addition, we verified ultrasound microbubble-mediated gene transfection improved miR-146a transfection efficacy.
肝缺血/再灌注损伤（IRI）是肝脏手术和移植中严重且常见的临床挑战。最近有报道称，微小RNA-146a（miR-146a）在肝IRI中表达异常，但其潜在机制尚未完全阐明。越来越多的证据表明，miR-146a靶向Toll样受体4（TLR4）信号通路。在此，我们发现miR-146a抑制TLR4信号通路，同时肝功能障碍、组织学损伤和炎症减轻。相反，抑制miR-146a会增加TLR4和白细胞介素-1受体相关激酶，同时加剧肝IRI和炎症。综上所述，这些数据表明miR-146a通过抑制TLR4信号通路来保护肝脏免受IRI损伤。此外，我们证实超声微泡介导的基因转染提高了miR-146a的转染效率。
