Department of Transplantation, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
Institute of Hepatobiliary Diseases, Transplant Center, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.
Apoptosis. 2022 Dec;27(11-12):899-912. doi: 10.1007/s10495-022-01757-6. Epub 2022 Aug 5.
Liver ischemia reperfusion injury (IRI) is a serious complication of certain liver surgeries, and it is difficult to prevent. As a potential drug-free treatment, mild hypothermia has been shown to promote positive outcomes in patients with IRI. However, the protective mechanism remains unclear. We established in vivo and in vitro models of hepatic ischemia reperfusion (IR) and mild hypothermia pretreatment. Hepatocytes were transfected with RNA-binding motif protein 3 (RBM3) overexpression plasmids, and IR was performed. Cell, culture medium, blood and tissue samples were collected to assess hepatic injury, oxidative stress, apoptosis and changes in RBM3 expression in the liver. Upregulation of RBM3 expression by mild hypothermia reduced the aminotransferase release, liver tissue injury and mitochondrial injury induced by liver IR. Hepatic IR-induced p38 and c-Jun N-terminal kinase (JNK) signaling pathway activation, oxidative stress injury and apoptosis could be greatly reversed by mild hypothermia. Overexpression of RBM3 mimicked the hepatoprotective effect of mild hypothermia. Mild hypothermia protects the liver from ischemia reperfusion-induced p38 and JNK signaling pathway activation, oxidative stress injury and apoptosis through the upregulation of RBM3 expression.
肝脏缺血再灌注损伤（IRI）是某些肝脏手术的严重并发症，难以预防。作为一种潜在的无药物治疗方法，轻度低温已被证明可促进 IRI 患者的积极结果。然而，其保护机制尚不清楚。我们建立了肝脏缺血再灌注（IR）和轻度低温预处理的体内和体外模型。转染 RNA 结合基序蛋白 3（RBM3）过表达质粒，进行 IR。收集肝细胞、培养液、血液和组织样本，以评估肝损伤、氧化应激、细胞凋亡以及肝脏中 RBM3 表达的变化。轻度低温上调 RBM3 表达可减轻肝脏 IR 引起的转氨酶释放、肝组织损伤和线粒体损伤。轻度低温可大大逆转肝脏 IR 诱导的 p38 和 c-Jun N-末端激酶（JNK）信号通路激活、氧化应激损伤和细胞凋亡。RBM3 的过表达模拟了轻度低温的肝保护作用。轻度低温通过上调 RBM3 表达来保护肝脏免受缺血再灌注诱导的 p38 和 JNK 信号通路激活、氧化应激损伤和细胞凋亡。
