Increased nitric oxide production in hepatocytes is involved in liver dysfunction following obstructive jaundice.
Increased nitric oxide production in hepatocytes is involved in liver dysfunction following obstructive jaundice.
复制标题
肝细胞中一氧化氮的产生增加与阻塞性黄疸后的肝功能障碍有关。
DOI：
10.1006/jsre.2002.6436
复制
发表时间：
2002
期刊：
影响因子：
--
通讯作者：
T. Okumura
中科院分区：
文献类型：
--
作者：
W. Tu;H. Kitade;S. Satoi;Zhong;M. Kaibori;A. Kwon;Y. Kamiyama;T. Okumura
背景
阻塞性黄疸会损害肝脏的关键功能。然而，肝功能障碍的机制尚不清楚。一氧化氮与各种病理条件下的肝损伤有关。我们之前报道过促炎细胞因子白细胞介素-1β（IL-1β）刺激肝细胞中一氧化氮的产生，这与线粒体功能障碍有关。进行研究以检查阻塞性黄疸是否影响肝细胞中一氧化氮的产生并改变肝脏能量代谢。
材料和方法
从阻塞性黄疸或假对照大鼠模型中分离并培养肝细胞。在 IL-1β 存在的情况下，比较两组之间的一氧化氮产量、ATP 含量和酮体比率（乙酰乙酸/β-羟基丁酸；KBR）。
结果
与假手术对照组相比，从梗阻性黄疸大鼠获得的肝细胞在 IL-1β 刺激下产生一氧化氮的水平显着增加。蛋白质印迹分析显示，一氧化氮生成的增强是翻译后事件，因为两组之间诱导型一氧化氮合酶（NOS）的蛋白质水平没有变化。 IL-1β 降低了梗阻性黄疸中的细胞 ATP 含量，但在假手术对照中则没有。此外，KBR（线粒体氧化还原状态的标志物）在梗阻性黄疸组中低于假手术对照组。添加 N(G)-单甲基-L-精氨酸（NOS 抑制剂）可消除 ATP 含量和 KBR 以及一氧化氮生成的下降。
结论
这些结果表明，阻塞性黄疸后一氧化氮产生的启动与部分通过线粒体功能障碍引起的肝脏能量代谢的改变有关。调节一氧化氮的产生可能是预防阻塞性黄疸肝功能障碍的有效疗法。
BACKGROUND
Obstructive jaundice damages critical functions in the liver. However, the mechanisms involved in hepatic dysfunction are obscure. Nitric oxide is implicated in liver injury under various pathological conditions. We previously reported that proinflammatory cytokine interleukin-1beta (IL-1beta) stimulated the production of nitric oxide in hepatocytes, which was associated with mitochondrial dysfunction. Studies were performed to examine whether obstructive jaundice influences the production of nitric oxide in hepatocytes and alters hepatic energy metabolism.
MATERIAL AND METHODS
Hepatocytes were isolated and cultured from a rat model of obstructive jaundice or sham control. Nitric oxide production, ATP content, and ketone body ratio (acetoacetate/beta-hydroxybutyrate; KBR) were compared between the two groups in the presence of IL-1beta.
RESULTS
Hepatocytes obtained from obstructive jaundice rats markedly increased the levels of nitric oxide production stimulated by IL-1beta compared with those from sham control. Western blot analysis revealed that the enhancement of nitric oxide production was a posttranslational event, since protein levels of inducible nitric oxide synthase (NOS) were unchanged between the two groups. IL-1beta decreased cellular ATP content in obstructive jaundice but not in sham control. Further, the KBR, which is a marker of mitochondrial redox state, was lower in obstructive jaundice than in sham control. Addition of N(G)-monomethyl-L-arginine, an inhibitor of NOS, abolished the decreases in ATP content and KBR as well as the nitric oxide production.
CONCLUSIONS
These results indicate that a priming of nitric oxide production following obstructive jaundice is associated with the alteration of hepatic energy metabolism in part through mitochondrial dysfunction. Regulation of nitric oxide production may be a useful therapy for preventing liver dysfunction in obstructive jaundice.
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IL-1β 在肝诱导型一氧化氮合酶的体外和体内调节中发挥核心作用。
DOI：
--
发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Geller,DA;deVera,ME;Russell,DA;Shapiro,RA;Nussler,AK;Simmons,RL;Billiar,TR
通讯作者：
Billiar,TR
影响因子：
2.9
作者：
GREEN, LC;WAGNER, DA;TANNENBAUM, SR
通讯作者：
TANNENBAUM, SR
影响因子：
--
作者：
STADLER, J;BILLIAR, TR;SIMMONS, RL
通讯作者：
SIMMONS, RL
影响因子：
29.4
作者：
Singer, II;Kawka, DW;Stenson, WF
通讯作者：
Stenson, WF
影响因子：
3.8
作者：
Ochoa, JB;Bernard, AC;Kearney, PA
通讯作者：
Kearney, PA