Rb1 postconditioning attenuates liver warm ischemia-reperfusion injury through ROS-NO-HIF pathway
Rb1 postconditioning attenuates liver warm ischemia-reperfusion injury through ROS-NO-HIF pathway
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DOI：
10.1016/j.lfs.2011.01.022
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发表时间：
2011-03-28
期刊：
影响因子：
6.1
通讯作者：
Li, Youping
中科院分区：
文献类型：
--
作者：
Guo, Yingjia;Yang, Tong;Li, Youping
目的：人参皂苷Rb 1能预防缺血性神经元死亡和局灶性脑缺血，但其对肝脏热I/R损伤的作用尚不明确。主要方法：采用小鼠肝中、左外叶缺血60 min，将小鼠分为假手术组、缺血再灌注组、Rb 1+缺血再灌注组（Rb 1后处理，20 mg/kg，缺血后腹腔注射）、假手术+ L-NAME组、I/R + L-NAME组和Rb 1 + I/R + L-NAME组。检测血清丙氨酸氨基转移酶（ALT）水平，并观察肝脏形态学变化。测定一氧化氮（NO）、一氧化氮合酶（NOS）含量、丙二醛（MDA）含量及超氧化物歧化酶（SOD）活性。Western blot和免疫组化检测Akt、p-Akt、iNOS、HIF-1 α、肿瘤坏死因子-α（TNF-α）和细胞间粘附分子-1（ICAM-1）的表达。Rb 1组ALT水平明显降低（p < 0.05）。Rb_1可显著提高血清NO、iNOS含量和肝组织SOD活性（p < 0.05），降低MDA含量（p <0.05）。Rb 1组p-Akt、iNOS和HIF-1 α蛋白表达明显增强。Rb 1后处理可显著抑制TNF-α和ICAM-1蛋白和mRNA的表达（p < 0.05）。这些保护作用可被L-NAME阻断。这些结果提示Rbl可能通过ROS-NO-HIF途径对肝脏热I/R损伤具有治疗潜力。(c)2011 Elsevier Inc. All rights reserved.
Aims: Ginsenoside Rb1 could prevent ischemic neuronal death and focal cerebral ischemia, but its roles to liver warm I/R injury remain to be defined. We determined if Rb1 would attenuate warm I/R injury in mice.Main methods: Mice were divided into sham, I/R, Rb1 + I/R (Rb1 postconditioning, 20 mg/kg, i.p. after ischemia), sham + L-NAME, I/R + L-NAME, and Rb1 + I/R + L-NAME groups using 60 min of the liver median and left lateral lobes ischemia. Serum levels of alanine aminotransferase (ALT) were measured and morphology changes of livers were evaluated. Contents of nitric oxide (NO) and nitric oxide synthase (NOS), malondialdehye (MDA) and activity of superoxide dismutase (SOD) were measured. Expressions of Akt, p-Akt, iNOS, HIF-1alpha, tumor necrosis factor-a (TNF-alpha) and intercellular adhesion molecule-1 (ICAM-1) were also determined by western blot or immunohistochemistry.Key findings: Rb1 postconditioning attenuated the dramatically functional and morphological injuries. The levels of ALT were significantly reduced in Rb1 group (p < 0.05). Rb1 upregulated the concentrations of NO, iNOS in serum, iNOS, and activity of SOD in hepatic tissues (p < 0.05), while it dramatically reduced the concentration of MDA (p < 0.05). Protein expressions of p-Akt, iNOS and HIF-1alpha were markedly enhanced in Rb1 group. Protein and mRNA expressions of TNF-alpha and ICAM-1 were markedly suppressed by Rb1 (p < 0.05).Significance: We found that Rb1 postconditioning could protect liver from I/R injury by upregulating the content of NO and NOS, and also HIF-1alpha protein expression. These protective effects could be abolished by L-NAME. These findings suggested Rbl may have the therapeutic potential through ROS-NO-HIF pathway for management of liver warm I/R injury. (c) 2011 Elsevier Inc. All rights reserved.