Heme oxygenase-1 could mediate the protective effects of hyperbaric oxygen preconditioning against hepatic ischemia-reperfusion injury in rats
Heme oxygenase-1 could mediate the protective effects of hyperbaric oxygen preconditioning against hepatic ischemia-reperfusion injury in rats
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DOI：
10.1111/j.1440-1681.2011.05560.x
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发表时间：
2011-10-01
影响因子：
2.9
通讯作者：
Deng, Xiao-Ming
中科院分区：
文献类型：
--
作者：
Liu, Yi;Sun, Xue-Jun;Deng, Xiao-Ming
1. 当肝脏遭受亚致死应激（例如缺血再灌注 (I/R) 损伤）时，血红素加氧酶 1 (HO-1) 在维持细胞稳态方面发挥着关键作用。在本研究中，我们研究了 HO-1 在高压氧 (HBO) 预处理中对 I/R.2 后肝损伤的保护作用。本研究采用大鼠全肝缺血（30 分钟）和再灌注（60 分钟）损伤模型。预处理组在诱导 I/R 损伤前 24 小时暴露于 HBO。其他组在 I/R 前 1 小时腹腔注射锌原卟啉 IX (ZnPP) 以抑制 HO-1 活性。再灌注期结束时，采集血液和肝脏样本，分析肝损伤标志物、形态学变化以及肝脏中HO-1的表达和活性。 3．在未经治疗的大鼠中，I/R 会导致肝损伤标志物增加，例如血浆转氨酶、炎症细胞因子（肿瘤坏死因子-α 和白介素-1β）和组织丙二醛。然而，HBO 预处理减弱了 I/R 诱导的这些肝损伤标志物的增加，并阻止了 I/R 损伤诱导的肝细胞坏死和凋亡。此外，HBO 预处理显着增加了肝脏中 HO-1 mRNA 和蛋白质水平。 ZnPP预处理抑制HO-1活性的大鼠，HBO预处理对I/R损伤的保护作用消失。4．总之，HBO 预处理可以保护肝脏免受 I/R 损伤，这种作用似乎可能是通过 HO-1 的诱导介导的。
1. Heme oxygenase 1 (HO-1) has been shown to play a pivotal role in the maintenance of cellular homeostasis when the liver undergoes sublethal stress, such as ischaemia-reperfusion (I/R) injury. In the present study, we investigated the protective role of HO-1 in hyperbaric oxygen (HBO) preconditioning against liver injury after I/R.2. A total hepatic ischaemia (30 min) and reperfusion (60 min) injury model in rats was used in the present study. Preconditioned groups were exposed to HBO 24 h prior to the induction of I/R injury. Other groups were injected with zinc protoporphyrin IX (ZnPP) intraperitoneally 1 h before I/R to inhibit HO-1 activity. At the end of the reperfusion period, blood and liver samples were collected for the analysis of liver injury markers, morphological changes, and HO-1 expression and activity in the liver.3. In untreated rats, I/R induced an increase in hepatic injury markers, such as plasma transaminases, inflammatory cytokines (tumour necrosis factor-alpha and interleukin-1 beta), and tissue malondialdehyde. However, HBO preconditioning attenuated the I/R-induced increases in these hepatic injury markers, and prevented both the necrosis and apoptosis of hepatocytes induced by I/R injury. Furthermore, HBO preconditioning significantly increased HO-1 mRNA and protein levels in the liver. In rats in which HO-1 activity had been inhibited with ZnPP pretreatment, the protective effects of HBO preconditioning against I/R injury were abolished.4. In conclusion, HBO preconditioning can protect the liver against I/R injury and it appears that this effect might be mediated by the induction of HO-1.