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Uncoupling protein 2 prevents ischaemia reperfusion injury through the regulation ROS/NF-κB signalling in mice.
Molecular Membrane Biology ( IF 2.857 ) Pub Date : 2020-01-27 , DOI: 10.1080/09687688.2019.1701720
Yaolei Zhang 1 , Xin Guo 1 , Ting Li 1 , Yaxing Feng 1 , Wei Li 1 , Xiaoyan Zhu 1 , Rui Gu 1 , Longfu Zhou 1
Affiliation  

Abstract

Background and objective: Renal ischaemia reperfusion injury (IRI), characterized by excessive cell apoptosis and inflammation, remains a clinical challenge. Mitochondrial membrane potential is related to apoptosis and inflammation of IRI. Previous studies have indicated that uncoupling protein 2 (UCP2) and its receptors play an important role in inflammation, apoptosis and injuries, especially in oxidative stress injury. However, the underlying mechanisms of UCP2 in IRI are still not fully understood.

Methods and results: In the present study, male C57 mice were randomly divided into three groups:sham, IR, and UCP2-/-+IR. The IRI model was established by removing the right kidney and clamping the left kidney for 45 min followed by reperfusion. Blood urea nitrogen (BUN) and creatinine were higher in UCP2-/-+IR mouse serum than in IR mouse serum. In addition, relative to the IR group, UCP2-/-+IR mouse renal cells had increased reactive oxygen species (ROS) production, aggravating tissue damage. We examined changes in the NFκB pathway and found that after UCP2 knockdown, IκB and IKK phosphorylation increased, and nuclear NFκB increased, which stimulated inflammation. Moreover, there was an increase in apoptosis in the UCP2-/-+IR group.

Conclusion: UCP2 can prevent IRI in C57 mice. Mechanistically, UCP2 may decrease ROS expression, NFκB activation and caspase-3 cleavage, rendering UCP2 a potential therapeutic target against IRI.



中文翻译:

解偶联蛋白2通过调节小鼠中的ROS /NF-κB信号传导来防止缺血再灌注损伤。

摘要

背景与目的:以细胞过度凋亡和炎症为特征的肾脏缺血再灌注损伤(IRI)仍然是临床挑战。线粒体膜电位与IRI的凋亡和炎症有关。先前的研究表明,解偶联蛋白2(UCP2)及其受体在炎症,细胞凋亡和损伤(尤其是氧化应激损伤)中起重要作用。但是,IRI中UCP2的基本机制仍未完全了解。

方法和结果:在本研究中,将雄性C57小鼠随机分为三组:假手术,IR和UCP2 -/- + IR。通过取出右肾并钳住左肾45分钟然后再灌注来建立IRI模型。UCP2 -/- + IR小鼠血清中的血尿素氮(BUN)和肌酐高于IR小鼠血清。此外,相对于IR组,UCP2 -/- + IR小鼠肾细胞具有增加的活性氧(ROS)产生,加剧了组织损伤。我们检查了NFκB途径的变化,发现在UCP2敲低后,IκB和IKK磷酸化增加,而核NFκB增加,从而刺激了炎症。而且,UCP2 -/-中的细胞凋亡增加+ IR组。

结论: UCP2可以预防C57小鼠的IRI。从机制上讲,UCP2可能会降低ROS表达,NFκB活化和caspase-3裂解,从而使UCP2成为抗IRI的潜在治疗靶标。

更新日期:2020-01-27
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