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The roles of gaseous mediators during inflammatory cytokine induced cardiac depression

气体介质在炎症细胞因子诱导的心脏抑制中的作用

基本信息

批准号：
14571471
负责人：
SAKAMOTO Atsuhiro
金额：
$ 2.3万
依托单位：
Nippon Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

<Basic research> Using the rat working heart preperation, the role and relation of gaseous molecules (nitric oxide, NO ; carbon monoxide, CO) during tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-Iβ) induced cardiac depression. Administration of cytokines depressed the left ventricular work (LVW). Administrations of NO synthase (NOS) inhibitor, L-canavanin (CAN) and CO synthase (hemeoxygenase) inhibitor, zinc protoporphyrine (ZPP) improved the LVW. Gene expressions of inducible NOS (iNOS) and inducible HO (HO-1) in the left ventricle significantly increased 2 hours after perfusion. Administration of CAN inhibited the increase of HO-1 expression, and adminstration, of ZPP inhibited the HO-1 expression and promoted the INOS expression. These data suggest that NOS/NO systema and HO/CO system are interrelated at the gene ezpression levels even when those systems are highly promoted, however, the interaction of both systems on cardiac contractility did not make clear and other factors are speculated to be important under those situation. <Clinical research> Changes in CO generation during coronary artery bypass graft by measuring CO-Hb concentrations and the expression of HO in circulating blood as well as the expressions of TNF-α and IL-1β. CO-Hb significantly increased after surgery ; however, those values did not significantly change in patients who showed CO-Hb 【greater than or equal】1.0% before surgery. The expression ratios of HO-1, TNF-α, and IL-1β significantly increased after surgery. CO-Hb significantly correlated with the expression ratios of the inflammatory mediators ; however, the correlation was low in the patients who showed CO-Hb 【greater than or equal】1.0% before surgery. These data indicate that CO-Hb can, in general, reflect the surgical inflammatory response ; however, the usefulness of CO-Hb as a marker of surgical stress might be limited to certain patients.

<Basic research>采用大鼠工作心脏模型，研究了一氧化氮（NO）、一氧化碳（CO）在肿瘤坏死因子-α（TNF-α）和白细胞介素-1 β（IL-1 β）引起的心脏抑制中的作用及相互关系。给予细胞因子抑制左心室作功（LVW）。NO合酶（NOS）抑制剂L-刀豆素（CAN）和CO合酶（血红素加氧酶）抑制剂锌原卟啉（ZPP）的给药改善了LVW。灌流后2 h，左室诱导型一氧化氮合酶（iNOS）和诱导型血红素氧合酶（HO-1）的基因表达明显增加。CAN抑制HO-1表达的增加，ZPP抑制HO-1表达，促进INOS表达。提示NOS/NO系统和HO/CO系统在基因表达水平上是相互关联的，即使在这两个系统被高度促进的情况下，但这两个系统在心肌收缩力方面的相互作用尚不清楚，推测在这种情况下，其他因素也是重要的。<Clinical research>通过测定冠状动脉旁路移植术中CO生成量、CO血红蛋白浓度、HO表达及TNF-α、IL-1β表达，探讨冠状动脉旁路移植术中CO生成量的变化。术后CO-Hb显著增加;然而，在术前CO-Hb [大于或等于]1.0%的患者中，这些值没有显著变化。HO-1、TNF-α和IL-1β的表达率在术后显著升高。CO-Hb与炎症介质的表达率显著相关;然而，在术前CO-Hb [大于或等于]1.0%的患者中，相关性较低。这些数据表明，CO-Hb可以，在一般情况下，反映手术炎症反应，然而，有用的CO-Hb作为标记的手术压力可能仅限于某些患者。