Induction of heme oxygenase-1 by hemin protects lung against orthotopic autologous liver transplantation-induced acute lung injury in rats.
Induction of heme oxygenase-1 by hemin protects lung against orthotopic autologous liver transplantation-induced acute lung injury in rats.
复制标题
血红素诱导血红素加氧酶-1 保护肺免受原位自体肝移植引起的大鼠急性肺损伤
DOI：
10.1186/s12967-016-0793-0
复制
发表时间：
2016-02-02
影响因子：
7.4
通讯作者：
Hei Z
中科院分区：
文献类型：
--
作者：
Chi X;Guo N;Yao W;Jin Y;Gao W;Cai J;Hei Z
肝移植后急性肺损伤（ALI）严重影响患者的生存，其机制尚不清楚，缺乏有效的治疗方法。作者推测，再灌注诱导的氧化应激增加在介导肝移植后ALI中起关键作用，而血红素氧化酶-1 （HO-1）的诱导，一种具有抗氧化应激特性的酶，可以有效地保护肺免受ALI的伤害。雄性Sprague-Dawley大鼠在没有或存在选择性HO-1诱导剂（Hemin）或HO-1抑制剂（ZnPP）治疗的情况下进行了自体原位肝移植（OALT）。术后8 h采集肺组织，评估病理评分和肺含水量；分析大鼠成活率；western blot检测HO-1蛋白表达，免疫荧光染色检测核因子-红细胞2相关因子- 2 （Nrf2）和核因子-κB p65的核易位。测定肺组织炎症因子和氧化指标。在早期即OALT后8 h采伐的肺中，Hemin处理显著提高了超氧化物歧化酶活性，降低了丙二醛、过氧化氢、白细胞介素-6、髓过氧化物酶和肿瘤坏死因子-α的产生，从而增加了HO-1蛋白的表达，降低了病理评分，提高了大鼠的存活率。潜在的机制可能与Nrf2的激活和NF-κB p65核转运的抑制有关。然而，ZnPP加重了这些变化。Hemin预处理通过增强HO-1诱导，提高肺抗氧化能力，减轻炎症应激，对oalt诱导的再灌注早期ALI具有保护作用。
Post-liver transplantation acute lung injury (ALI) severely affects patients’ survival, whereas the mechanism is unclear and effective therapy is lacking. The authors postulated that reperfusion-induced increased oxidative stress plays a critical role in mediating post-liver transplantation ALI and that induction of heme oxgenase-1 (HO-1), an enzyme with anti-oxidative stress properties, can confer effective protection of lung against ALI. Male Sprague–Dawley rats underwent autologous orthotopic liver transplantation (OALT) in the absence or presence of treatments with the selective HO-1 inducer (Hemin) or HO-1 inhibitor (ZnPP). Lung tissues were collected at 8 h after OALT, pathological scores and lung water content were evaluated; survival rate of rats was analyzed; protein expression of HO-1 was determined by western blotting, and nuclear translocation of Nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor(NF)-κB p65 were detected by Immunofluorescence staining. The inflammatory cytokines and oxidative indexes of lung tissue were determined. In lungs harvested at the early stage i.e. 8 h after OALT, Hemin treatment significantly increased superoxide dismutase activities, and reduced malondialdehyde, hydrogen peroxide, interleukin-6, myeloperoxidase, and tumor necrosis factor-α production,which were associated with increased HO-1 protein expression and lower pathological scores and increased survival rate of rats. The underline mechanisms might associate with activation of Nrf2 and inhibition of NF-κB p65 nuclear translocation. However, these changes were aggravated by ZnPP. Hemin pretreatment, by enhancing HO-1 induction, increased lung antioxidant capacity and reduced inflammatory stress,protected the lung from OALT-induced ALI at early stage of reperfusion.