ROS homeostasis, a key determinant in liver ischemic-preconditioning.
ROS homeostasis, a key determinant in liver ischemic-preconditioning.
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DOI：
10.1016/j.redox.2017.04.036
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发表时间：
2017-08
期刊：
影响因子：
11.4
通讯作者：
Monsalve M
中科院分区：
文献类型：
--
作者：
Prieto I;Monsalve M
ROS是缺血再灌注损伤的关键介质，但也是诱导应激反应所必需的，从而限制组织损伤，并支持缺血预适应方案所提供的保护。肝脏脂肪变性是肝移植失败的重要危险因素。肝脏脂肪变性与线粒体功能障碍和线粒体ROS的过度产生有关。旨在降低脂肪变性肝脏对缺血-再灌注损伤敏感性的研究表明，脂肪变性肝脏对这些预适应方案的反应能力降低。最近的研究表明，这些效应与脂肪变性肝脏通过诱导代偿反应来应对再灌注后升高的ROS水平的能力降低有关。这种对ROS的反应失败与抗氧化剂水平降低、线粒体损伤、肝细胞死亡、免疫系统激活和促纤维化介质的诱导有关。正常肝脏和脂肪变性肝脏对IR的反应。在正常肝脏中诱导抗氧化系统有助于对预适应方案的反应而存活。脂肪变性肝脏中PGC-1α活性降低限制了抗氧化剂的诱导，并导致广泛的肝细胞死亡。IR，即缺血再灌注；IPC，即缺血预适应；ROS，即活性氧。
Reactive Oxygen Species (ROS) are key mediators of ischemia-reperfusion injury but also required for the induction of the stress response that limits tissue injury and underlies the protection provided by ischemic-preconditioning protocols. Liver steatosis is an important risk factor for liver transplant failure. Liver steatosis is associated with mitochondrial dysfunction and excessive mitochondrial ROS production. Studies aiming at decreasing the sensibility of the steatotic liver to ischemia-reperfusion injury using pre-conditioning protocols, have shown that the steatotic liver has a reduced capacity to respond to these protocols. Recent studies indicate that these effects are related to a reduced capacity of the steatotic liver to respond to elevated ROS levels following reperfusion by inducing a compensatory response. This failure to respond to ROS is associated with reduced levels of antioxidants, mitochondrial damage, hepatocyte cell death, activation of the immune system and induction of pro-fibrotic mediators. Response to IR in normal vs steatotic liver. Induction of antioxidant systems in the normal liver facilitates survival in response to preconditioning protocols. Reduced PGC-1α activity in the steatotic liver limits antioxidant induction and results in extensive hepatocyte cell death. IR, Ischemia-Reperfusion; IPC, Ischemic Preconditioning; and ROS, Reactive Oxygen Species.