在一种肺移植缺血再灌注模型中,MAPK可介导大鼠肺微血管内皮细胞中的炎症反应和细胞死亡

MAPK mediates inflammatory response and cell death in rat pulmonary microvascular endothelial cells in an ischemia-reperfusion model of lung transplantation
作者:Tan, J., Liu, D., Lv, X., Wang, L., Zhao, C., Che,
机构: 哈尔滨医科大学第二附属医院麻醉科
期刊: J HEART LUNG TRANSPL2013年8月2期81卷

Department of Anesthesiology, Second Affiliated Hospital, Harbin Medical University, No.194, XueFu Road, NanGang District, Harbin 150081, Heilongjiang Province, China 

Abstract

Background Hypoxia-reoxygenation of cultured macrovascular endothelial cells is used to study ischemia-reperfusion (IR)-related cellular and molecular changes; however, these models do not accurately depict events in pulmonary microvascular endothelial cells (PMVECs) during conventional lung retrieval and transplantation. We used rat PMVECs in a new non-hypoxic cell-based lung transplantation model to assess these events. Methods To simulate cold storage, rat PMVECs were preserved in 95% O2-5% CO2 at 4 C for 6 hours in low-potassium dextran solution. Dishes were warmed for 1 hour to room temperature for simulating implantation. Medium was added at 37 C in 50% O 2-5% CO2-45% N2 to simulate reperfusion. Additional PMVECs were transfected with siRNA targeting mitogen-activated protein kinases (MAPKs) and then subjected to simulated IR. Results MAPKs and NF-κB were activated during simulated reperfusion, and AP-1 was activated during ischemia and reperfusion. Increased malondialdehyde levels were found during cold ischemia, and apoptosis and production of IL-1β, IL-6, and TNF-α were observed during reperfusion. Silencing of MAPKs attenuated oxidative stress, inflammation and apoptosis. Silencing of JNK and p38 decreased NF-κB phosphorylation and increased inhibitor of NF-κB (IκB)α levels. Knockdown of ERK1/2 increased NF-κB phosphorylation but had no effect on IκBα expression. Silencing of JNK and ERK1/2, but not p38, decreased AP-1 phosphorylation. Conclusions Exposing rat PMVECs to simulated non-hypoxic IR caused lipid peroxidation, inflammation and apoptosis, which required MAPK-mediated NF-κB and AP-1 activation and distinct regulation of MAPKs by these 2 transcription factors. This model could be used to uncouple mechanisms of IR and evaluate potential therapeutics in alleviating IR injury.

 

通讯作者:Cui, X.; Department of Anesthesiology, Second Affiliated Hospital, Harbin Medical University, No.194, XueFu Road, NanGang District, Harbin 150081, Heilongjiang Province, China; email:cuixiaoguang66@yahoo.cn
学科代码:呼吸病学   关键词:activator protein-1; ischemia-
来源: Scopus
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