Intestinal NF-E2-related factor-2 expression and antioxidant activity changes in rats undergoing orthotopic liver autotransplantation.

Intestinal NF-E2-related factor-2 expression and antioxidant activity changes in rats undergoing orthotopic liver autotransplantation.
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DOI:
10.3892/ol.2013.1576
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发表时间:
2013-11
期刊:
影响因子:
2.9
通讯作者:
Hei Z
Hei Z
中科院分区:
医学4区
文献类型:
--
作者:
Ge M;Chi X;Zhang A;Luo G;Sun G;Xie H;Hei Z

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众所周知,肝移植会引起肠道损伤。活性氧(reactive oxygen species, ROS)诱导的氧化损伤在缺血再灌注损伤中起着至关重要的作用。nf - e2相关因子-2 (Nrf2)及其调控的抗氧化酶构成了清除ROS的关键内源性抗氧化系统。本研究探讨原位肝自体移植(OLAT)术后肠道ROS水平、Nrf2表达及抗氧化酶活性的动态变化。将Sprague-Dawley大鼠随机分为5组,分别为1个假手术组和4个OLAT组,分别于4、8、16、24 h进行评价。采集大鼠肠道标本进行组织病理学检查,检测过氧化氢(H2O2)、羟基自由基(•OH)、丙二醛(MDA)、还原性谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)水平及Nrf2表达。本研究表明,OLAT可导致严重的肠道损伤,表现为早在治疗后4 h肠道病理评分发生显著变化,8 h达到峰值。H2O2、•OH和MDA水平升高也反映了氧化应激。处理后4和8 h, SOD和CAT活性显著降低,GSH水平显著降低。在处理后16和24 h,各项参数逐渐恢复。在OLAT后4、16和24 h,小肠组织中Nrf2的表达显著升高。本研究表明,氧化剂和抗氧化剂之间的失衡有助于肠道氧化损伤,Nrf2的上调不足以抵御OLAT后的肠道氧化损伤。
Liver transplantation is known to trigger intestinal injuries. Oxidative damage that is induced by reactive oxygen species (ROS) plays a crucial role in ischemia-reperfusion injuries. NF-E2-related factor-2 (Nrf2) and its modulated antioxidant enzymes form the critical endogenous antioxidant system to scavenge ROS. The present study investigated the dynamic changes of intestinal ROS levels, Nrf2 expression and antioxidant enzyme activity following orthotopic liver autotransplantation (OLAT). Sprague-Dawley rats were randomly divided into five groups consisting of one sham group and four groups with rats that underwent OLAT and were evaluated following 4, 8, 16 and 24 h, respectively. The intestinal specimens were collected for histopathological examination and the detection of hydrogen peroxide (H2O2), hydroxyl radical (•OH), malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels and the expression of Nrf2. The present study demonstrated that OLAT resulted in severe intestinal injury, which manifested as a significant change in the intestine pathological scores as early as 4 h and peaking at 8 h post-treatment. Oxidative stress was also revealed by the increase of the H2O2, •OH and MDA levels. Significant decreases were observed in the activity of SOD and CAT and a dramatic decrease occurred in the levels of GSH at 4 and 8 h post-treatment. All the parameters were restored gradually at 16 and 24 h post-treatment. The expression of Nrf2 in the intestinal tissues increased significantly at 4, 16 and 24 h following OLAT. The present study shows that an imbalance between oxidants and antioxidants contributes to intestinal oxidative injury, and that the upregulation of Nrf2 is not sufficient to withstand intestinal oxidative injury following OLAT.
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