Alleviation of Ischemia-Reperfusion Injury in Liver Steatosis by Augmenter of Liver Regeneration Is Attributed to Antioxidation and Preservation of Mitochondria
Alleviation of Ischemia-Reperfusion Injury in Liver Steatosis by Augmenter of Liver Regeneration Is Attributed to Antioxidation and Preservation of Mitochondria
复制标题
肝脏再生促进剂减轻肝脏脂肪变性缺血再灌注损伤归因于抗氧化和线粒体保护
DOI：
10.1097/tp.0000000000001874
复制
发表时间：
2017-10-01
期刊：
影响因子：
6.2
通讯作者：
An, Wei
中科院分区：
文献类型：
--
作者：
Weng, Junhua;Li, Wen;An, Wei
背景脂肪肝是肝脏手术和肝移植的主要障碍之一，因为脂肪变性的肝细胞更容易受到缺血再灌注损伤（IRI）的影响。本研究观察了肝再生增强因子（ALR）对脂肪变性小鼠肝脏IRI的影响。方法.在体内，通过喂养蛋氨酸胆碱缺乏的饮食2周来诱导小鼠的肝脏脂肪变性。在肝部分温热IRI前三天，用含ALR的腺病毒转染小鼠。在体外研究中，分析了缺氧/复氧（HR）处理后ALR对脂肪变性HepG 2细胞的保护作用。结果将ALR基因转染到脂肪变性小鼠中可减轻肝损伤，抑制肝氧化应激，增加抗氧化能力，促进肝再生，从而抑制细胞凋亡/死亡。此外，与载体转染的细胞相比，ALR转染的细胞对HR损伤的抗性显著增加。HR诱导的线粒体活性氧升高减少，细胞抗氧化活性增强。ALR转染抑制了细胞凋亡，其机制可能与线粒体膜电位的保持、氧消耗速率的增加和腺苷三磷酸的产生有关。结论. ALR通过减轻氧化应激和线粒体功能障碍以及改善抗氧化作用来保护脂肪变性肝细胞免受IRI。ALR可作为一种潜在的治疗药物，用于脂肪肝的手术和移植。
Background. Fatty liver is one of the major impediments to liver surgery and liver transplantation because steatotic hepatocytes are more susceptible to ischemia-reperfusion injury (IRI). In this study, the effects of augmenter of liver regeneration (ALR) on hepatic IRI in steatotic mice were investigated. Methods. In vivo, liver steatosis of mice was induced by feeding a methionine-choline-deficient diet for 2 weeks. Three days before hepatic partial warm IRI, mice were transfected with the ALR-containing adenovirus. In an in vitro study, the protective effect of ALR on steatotic HepG2 cells was analyzed after hypoxia/reoxygenation (HR) treatment. Results. The transfection of the ALR gene into steatotic mice attenuated liver injury, inhibiting hepatic oxidative stress, increasing antioxidation capacities, promoting liver regeneration, and consequently suppressing cell apoptosis/death. Furthermore, resistance to HR injury was notably increased in ALR-transfected cells compared with the vector-transfected cells. The HR-induced rise in the mitochondrial reactive oxygen species was reduced, and cellular antioxidant activities were enhanced. The ALR transfection prevented cells from apoptosis, which can be attributed to the preservation of the mitochondrial membrane potential, enhancement of oxygen consumption rate and production of adenosine triphosphate. Conclusions. ALR protects steatotic hepatocytes from IRI by attenuating oxidative stress and mitochondrial dysfunction, as well as improving antioxidant effect. ALR may be used as a potential therapeutic agent when performing surgery and transplantation of steatotic liver.