Xu Yiping, Chen Yili, Yao Mengxia, You Yisheng, Nie Bin, Zeng Meina, Jiang Hui
Department of Anesthesiology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province, China.
Dose Response. 2023 Apr 11;21(2):15593258231169805. doi: 10.1177/15593258231169805. eCollection 2023 Apr-Jun.
Hepatic ischemia-reperfusion injury (HIRI)-induced acute lung injury (ALI) is characterized by high incidence and poor prognosis. The regulatory role of microRNA-146a (miR-146a) in HIRI has been reported, but if miR-146a could affect the progression of HIRI-induced ALI has not been reported. The mice HIRI model was established by ligating left hepatic portal vein and hepatic artery for 60 minutes and then treating with reperfusion for 4 hours. Hypoxia-reoxygenation (HR) was performed to establish cell model. The binding site between miR-146a and Peroxidase 1 (PRDX1) was predicted and validated. The levels of inflammation factors and redox markers were detected with commercial kits. Significant lower expression of miR-146a and higher expression of PRDX1 in HIRI animal model were observed. miR-146a inhibited the liver injury after HIRI induction through targeting PRDX1. miR-146a inhibited the lung injury caused by HIRI via regulating PRDX1. The inhibition of cell apoptosis and inflammation factors by miR-146a were reversed by pcDNA-PRDX1. This research demonstrated that miR-146a improved ALI caused by HIRI by inhibiting apoptosis, inflammation, oxidative condition through targeting PRDX1. This study might provide a novel thought for the prevention and treatment of ALI caused by HIRI by regulating miR-146a/PRDX1 axis.
肝缺血再灌注损伤（HIRI）诱导的急性肺损伤（ALI）具有发病率高和预后差的特点。已有报道称微小RNA-146a（miR-146a）在HIRI中具有调节作用，但miR-146a是否会影响HIRI诱导的ALI的进展尚未见报道。通过结扎左肝门静脉和肝动脉60分钟，然后进行4小时的再灌注，建立小鼠HIRI模型。进行缺氧复氧（HR）以建立细胞模型。预测并验证了miR-146a与过氧化物酶1（PRDX1）之间的结合位点。使用商用试剂盒检测炎症因子和氧化还原标志物的水平。在HIRI动物模型中观察到miR-146a表达显著降低，PRDX1表达升高。miR-146a通过靶向PRDX1抑制HIRI诱导后的肝损伤。miR-146a通过调节PRDX1抑制HIRI引起的肺损伤。pcDNA-PRDX1逆转了miR-146a对细胞凋亡和炎症因子的抑制作用。本研究表明，miR-146a通过靶向PRDX1抑制细胞凋亡、炎症和氧化状态，从而改善HIRI引起的ALI。本研究可能为通过调节miR-146a/PRDX1轴预防和治疗HIRI引起的ALI提供新思路。
