Autophagy lessens ischemic liver injury by reducing oxidative damage.
Autophagy lessens ischemic liver injury by reducing oxidative damage.
复制标题
自噬通过减少氧化损伤来减轻缺血性肝损伤
DOI：
10.1186/2045-3701-3-26
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发表时间：
2013-06-10
影响因子：
7.5
通讯作者：
Wei L
中科院分区：
文献类型：
--
作者：
Sun K;Xie X;Liu Y;Han Z;Zhao X;Cai N;Zhang S;Song J;Wei L
肝缺血/再灌注是一个多因素的过程，可导致肝损伤。据报道，仅缺血就足以引起肝损伤。营养剥夺是影响肝脏缺血性损伤的重要因素。因此，我们通过肝缺血大鼠体内模型和体外无营养模型来探讨自噬在缺血中的作用。结果体外激活的自噬在体内缺血和营养剥夺中均有发生，抑制自噬可加重缺血或营养缺乏引起的损伤。在无营养条件下，自噬抑制通过促进活性氧（ROS）积累而促进肝细胞坏死而非凋亡，而抗氧化剂NAC可以逆转这一趋势。抑制自噬也导致缺血大鼠肝脏坏死细胞百分比增加，但凋亡细胞百分比未增加。进一步研究表明，在营养剥夺的情况下，自噬抑制促进了线粒体ROS的产生，进一步加重了线粒体的损伤。这些变化形成了加速细胞坏死过程的“恶性循环”。自噬抑制还会增加肝脏缺血时线粒体氧化应激，抗氧化剂可抑制自噬抑制剂联合治疗对缺血肝损伤的加重。结论自噬通过减少ros诱导的肝坏死来抑制缺血性肝损伤。这一发现将有助于肝脏手术前治疗策略的发展。
BackgroundHepatic ischemia/reperfusion is a multi-factorial process which causes liver injury. It is reported that ischemia alone is sufficient to induce liver injury. Nutrient deprivation is a crucial factor impacting ischemic injury of the liver. Therefore, we explored the role of autophagy in ischemia through using hepatic ischemia rat modelin vivoand nutrient-free modelin vitro.ResultsWe found that both ischemiain vivoand nutrient deprivationin vitroactivated autophagy, inhibition of which aggravated ischemia- or nutrient deficiency-induced injury. In the nutrient-free condition, autophagy inhibition enhanced liver cell necrosis but not apoptosis by promoting reactive oxygen species (ROS) accumulation, and antioxidant NAC could reverse this trend. Inhibition of autophagy also resulted in the increase of the percentage of necrotic cell but not apoptotic cell in the ischemia-treated rat livers. Further studies showed that under nutrient deprivation, autophagy inhibition promoted mitochondrial ROS generation, which further aggravated mitochondria damage. These changes formed a “vicious cycle” that accelerated the process of cell necrosis. Autophagy inhibition also increased mitochondrial oxidative stress during hepatic ischemia, and antioxidant could suppress the aggravation of ischemia-induced liver damage in the co-treatment of autophagy inhibitor.ConclusionsTaken together, our results suggested that autophagy suppressed ischemic liver injury by reducing ROS-induced necrosis. This finding will contribute to the development of the therapeutic strategy about the pre-treatment of liver surgery.
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影响因子：
64.8
作者：
Scaffidi, P;Misteli, T;Bianchi, ME
通讯作者：
Bianchi, ME
影响因子：
13.3
作者：
Wang, Pei;Guan, Yun-Feng;Miao, Chao-Yu
通讯作者：
Miao, Chao-Yu
影响因子：
4.8
作者：
Santos, JH;Hunakova, L;Van Houten, B
通讯作者：
Van Houten, B
影响因子：
2.4
作者：
Suzuki T;Yoshidome H;Kimura F;Shimizu H;Ohtsuka M;Takeuchi D;Kato A;Furukawa K;Yoshitomi H;Iida A;Dochi T;Miyazaki M
通讯作者：
Miyazaki M
影响因子：
3.7
作者：
Park J;Lee J;Choi C
通讯作者：
Choi C