Hypoxia preconditioning induced HIF-1α promotes glucose metabolism and protects mitochondria in liver I/R injury
Hypoxia preconditioning induced HIF-1α promotes glucose metabolism and protects mitochondria in liver I/R injury
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DOI：
10.1016/j.clinre.2014.12.012
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发表时间：
2015-10-01
影响因子：
2.7
通讯作者：
Xu Kesen
中科院分区：
文献类型：
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作者：
Zhuang Zhuonan;Guo Sen;Xu Kesen
背景：缺血再灌注损伤（I/R）是肝移植术后的主要损伤之一。本研究旨在探讨低氧诱导的HIF-1 α通过促进糖代谢、减轻线粒体损伤和凋亡对大鼠移植肝I/R损伤的保护作用。结果：缺氧90 min后，缺氧诱导的HIF-1 α在肝组织中表达明显增加（HP vs. Ctrl，*P < 0.001）。术后肝组织中HIF-1 α的表达也维持在较高水平。在术后24 h，几种基因的水平得到提高，例如HK-2（HP vs. AT，24 h，*P = 0.004）、乳酸脱氢酶（LDHA）（HP vs. AT，24 h，* P = 0.003）、丙酮酸脱氢酶激酶（PDK-1）（HP vs. AT，24 h，* P = 0.007），甚至NF-κ B和Erk途径。TUNEL法显示，缺氧预处理后12 h肝组织细胞凋亡率较非缺氧预处理组明显降低。HP组的cleaved-caspase 3（HP vs. AT，* P = 0.0119）和PARP（HP vs. AT，* P = 0.0134）的表达也明显低于AT组。结论：缺氧诱导的HIF-1 α可促进糖代谢，保护肝细胞线粒体免受损伤。这可能是一种有效的保护肝脏免受I/R损伤和炎性损伤，特别是促进移植功能恢复的方法。(C)2015年Elsevier Masson SAS。All rights reserved.
Background: Ischemia and reperfusion (I/R) injury is one of the main lesions after liver transplantation. This study aims to detect hypoxia-induced HIF-1 alpha protects transplanted liver against I/R injury by promoting glucose metabolism to decrease mitochondrial injury and apoptosis on rat model.Methods: The rats were given a treatment of 90 min non-lethal hypoxic preconditioning to induce and increase the HIF-1 alpha expression. The autologous orthotopic liver transplantation model was used to imitate liver I/R injury.Results: Hypoxic-induced HIF-1 alpha was detected to increase in liver tissue after 90-minute hypoxic environment (HP vs. Ctrl, *P < 0.001). After operation, the expression of HIF-1 alpha in liver tissue was also stayed at a high level. At 24 h after operation, several genes were promoted, such as the levels of HK-2 (HP vs. AT, 24 h, *P = 0.004), Lactate dehydrogenase (LDHA) (HP vs. AT, 24 h, * P = 0.003), pyruvate dehydrogenase kinase (PDK-1) (HP vs. AT, 24 h, * P = 0.007), even the NF-kappa B and Erk pathways. From the TUNEL assay, the apoptosis in hypoxic preconditioning liver tissue was decreased compared with non-HP operative group at 12 h after operation. The expressions of cleaved-caspase 3 (HP vs. AT, * P = 0.0119) and PARP (HP vs. AT, * P = 0.0134) in HP group were also significantly lower than AT group.Conclusion: The hypoxia-induced HIF-1 alpha could promote glucose metabolism to protect hepato-cellular mitochondria from damage. It could be a useful way to protect liver against I/R injuries and inflammatory injury, and particularly promote the recovery of graft function. (C) 2015 Elsevier Masson SAS. All rights reserved.