Analysis of the metabolic disorder based on the redox theory in the septic patient induced by nitric oxide

基于氧化还原理论的一氧化氮所致脓毒症患者代谢紊乱分析

• 批准号: 10671227
• 负责人: KANEMAKI Toshiki
• 金额: $ 0.32万
• 依托单位: KANSAI MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671227/
• 关键词: Nitric Oxide; NO analyzer; ketore body ratio; redox theory; hepatocyte; liver dysfunction; primary culture; sepsis

Nitric oxide (NO) production in primary cultured rat hepatocytes were observed for 2 hours using the NO monitor. These findings were the same as nitrite measured by Griess reagent method. However, after 2 hours, we would not detected the NO. The attachment of the hepatocytes to the NO monitor affected the measurement.Nitric oxide production and its effect on energy metabolism was investigated in cultured rat hepatocytes obtained from the liver remnant after partial hepatectomy. The hepatocytes obtained from liver remnant after partial hepatectomy (HPH) produced more nitric oxide than hepatocytes obtained from sham operated liver (HS), following stimulation with IL-1β. In our recent study, IL-1β was shown to stimulate nitric oxide (NO) production in cultured rat hepatocytes and NO reduced the ketone body ratio (KBR : acetoacetate/b-hydroxybutyrate). The reduced KBR, reflecting the liver mitochondrial redox state (NADィイD1+ィエD1/NADH), resulted in the inhibition of ATP synthesis. In the present study, KBR in the medium of cultured HPH was lower than that of HS. Furthermore, adenine nucleotides content (ATP, ADP and AMP) was lower in HPH than in HS. These results suggest that following partial hepatectomy, the liver is more susceptible to mitochondrial dysfunction as a result of the nitric oxide produced during infection. The similar results ware observed in hepatocytes obtained from obstructive jaudice rat.In conclusion, hepatocytes in the liver remnant after partial hepatectomy demonstrated increased NO production which was attributed to increased sensitivity to IL-1βNO in turn, cause liver dysfunction after hepatectomy because NO induces hepatic mitochondria dysfunction.

使用NO监测器观察原代培养的大鼠肝细胞中的一氧化氮（NO）产生2小时。这些结果与Griess试剂法测定亚硝酸盐的结果一致。然而，2小时后，我们不会检测到NO。肝细胞的附着到NO monitored affected the measurement.Nitric oxide production及其对能量代谢的影响进行了研究，在培养的大鼠肝细胞中获得的肝部分切除术后的残余。用IL-1β刺激后，从部分肝切除术后的肝残体（HPH）获得的肝细胞比从假手术肝（HS）获得的肝细胞产生更多的一氧化氮。在我们最近的研究中，IL-1β显示刺激培养的大鼠肝细胞中一氧化氮（NO）的产生，并且NO降低酮体比率（KBR：乙酰乙酸/b-羟基丁酸）。还原的KBR反映了肝脏线粒体的氧化还原状态（NAD + NAD + D1/NADH），导致ATP合成的抑制。在本研究中，培养HPH的培养基中的KBR低于HS。此外，腺嘌呤核苷酸含量（ATP，ADP和AMP）HPH低于HS。这些结果表明，部分肝切除术后，肝脏更容易受到感染过程中产生的一氧化氮的结果线粒体功能障碍。梗阻性黄疸大鼠肝细胞中也观察到类似的结果。结论：肝部分切除术后肝细胞NO产生增加，这可能是由于肝细胞对IL-1β-NO敏感性增加，进而导致肝切除术后肝功能障碍，其原因是NO诱导肝线粒体功能障碍。

项目成果

Tu Wei: "An Enhancement of Nitric Oxide Production Regulates Energy Metabolism in Rat Hepatocytes after a Partial Hepatectomy"Journal of Hepatology. 30. 944-950 (1999)

涂伟：“一氧化氮生成的增强调节部分肝切除术后大鼠肝细胞的能量代谢”肝脏病学杂志。

Satoi S, Kamimaya Y, Kitade H, Kwon A-H, Takahashi K, Tu Wei, Inoue T, Takahashi H: "Nitric Oxide Production and Hepatic Dysfunction in Patients with Postoperative Sepsis."Clinical and Experimental Pharmacology and Physiology. (in press). (2000)

Satoi S、Kamimaya Y、Kitade H、Kwon A-H、Takahashi K、Tu Wei、Inoue T、Takahashi H：“术后脓毒症患者的一氧化氮产生和肝功能障碍。”临床和实验药理学和生理学。