Protective effect of liver ischemic preconditioning on liver and lung injury induced by hepatic ischemia-reperfusion in the rat
Protective effect of liver ischemic preconditioning on liver and lung injury induced by hepatic ischemia-reperfusion in the rat
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DOI：
10.1002/hep.510300622
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发表时间：
1999-12-01
期刊：
影响因子：
13.5
通讯作者：
Roselló-Catafau, J
中科院分区：
文献类型：
--
作者：
Peralta, C;Prats, N;Roselló-Catafau, J
本研究评估预处理是否可以通过抑制肝缺血再灌注（I/R）后肿瘤坏死因子（TNF）的释放来调节肿瘤坏死因子（TNF）对肝和肺的损伤作用。缺血前用氯化钆（GdCl3）抑制Kupffer细胞释放肝脏TNF，使TNF维持在控制水平，减轻转氨酶、血管通透性和与肝I/R损伤相关的水肿的增加；添加TNF逆转了这种有益作用，表明主要从库普弗细胞释放的TNF在肝L/R损伤中的意义。预处理阻止了肝脏TNF的增加，从而减轻了肝损伤，而TNF的添加则抵消了预处理的益处。对一氧化氮（NO）合成的抑制消除了预处理的影响，而GdCl3的加入避免了NO抑制的伤害作用。此外，在VR前给药NO提供了与预处理相似的结果，而添加TNF则消除了NO的益处。因此，预处理对肝脏VR后TNF释放的影响是由NO介导的。GdCl3抑制Kupffer细胞的肝脏TNF释放，可阻止血浆TNF的增加和肝I/R后肺的损伤作用，这些作用在添加TNF后恢复。预处理导致肝脏TNF水平降低，阻止全身TNF释放，从而减轻肝I/R后的肺损伤。然而，TNF的加入取消了预处理对肺损伤的保护作用。这些研究结果表明，预处理可以减轻Kupffer细胞的肝缺血后TNF释放，从而可能减轻肝I/R后的肝和肺损伤，并且这种预处理的作用是由NO介导的。
This study evaluates whether preconditioning could modulate the injurious effects of tumor necrosis factor (TNF) on liver and lung following hepatic ischemia-reperfusion (I/R) by inhibiting hepatic postischemic TNF release. The inhibition of hepatic TNF release from Kupffer cells with gadolinium chloride (GdCl3) previous to ischemia maintained TNF at control levels, attenuating the increases in transaminases, vascular permeability, and edema associated with hepatic I/R injury; TNF addition reverted this beneficial effect, indicating the implication of the TNF released mainly from Kupffer cells in hepatic L/R injury. Preconditioning prevented hepatic TNF increases, thus attenuating the liver injury, while TNF addition abolished the benefits of preconditioning. Inhibition of nitric oxide (NO) synthesis abolished the effect of preconditioning, whereas GdCl3 addition avoided the injurious effect of NO inhibition. In addition, NO administration before VR offered similar results to those found in preconditioning, while TNF addition abolished the benefits of NO. Thus, the effect of preconditioning on TNF release after hepatic VR is mediated by NO. Inhibition of hepatic TNF release from Kupffer cells with GdCl3 prevented both the increase in plasma TNF and the injurious effect in lung seen after hepatic I/R, and these effects were reverted with TNF addition. Preconditioning resulting in reduced hepatic TNF levels prevented the systemic TNF release, thus reducing the lung damage following hepatic I/R, However, TNF addition abolished the protective effect of preconditioning on lung injury. These findings indicate that preconditioning attenuates hepatic postischemic TNF release from Kupffer cells, thus probably reducing the liver and lung injury following hepatic I/R, and that this effect of preconditioning is mediated by NO.