Heme oxygenase-dependent carbon monoxide production is a hepatic adaptive response to sepsis
Heme oxygenase-dependent carbon monoxide production is a hepatic adaptive response to sepsis
复制标题
DOI：
10.1006/jsre.1997.5135
复制
发表时间：
1997-07-15
影响因子：
2.2
通讯作者：
Garrison, RN
中科院分区：
文献类型：
--
作者：
Downard, PJ;Wilson, MA;Garrison, RN
脓毒症的血流动力学效应部分归因于一氧化氮（NO）产生增加和鸟苷酸环化酶激活，导致cGMP增加和血管平滑肌松弛。血红素加氧酶-1（HO-1）是一种热休克蛋白，已被证明通过形成一氧化碳（CO）来增加细胞内cGMP水平。我们推测HO可能是肝脏对感染反应的重要介质。雄性Swiss韦伯斯特小鼠进行标准盲肠结扎和穿刺（CLP，18 gauge 2X）或假手术，并接受生理盐水（NS）或Zn原卟啉IX（ZN PP IX），一种竞争性HO抑制剂（n = 6-8/组）。在3、6、12和24小时从单独的小鼠中收集肝组织样品。在3和24小时收集血清。半定量逆转录聚合酶链反应方法用于测量HO-1 mRNA水平。通过ELISA测量肝cGMP水平。重复分组（n = 10/组）以评估死亡率。在3和24小时收集血清以测量血清天冬氨酸转氨酶（AST）水平。HO-1 mRNA表达在CLP后3小时显著增加（P < 0.05），HO抑制剂单独作用时也显著增加（P < 0.05）。HO-1 mRNA在24小时内仍持续升高，与CLP +生理盐水组相比，HO抑制组CLP动物24小时肝cGMP含量显著降低（P < 0.05），CLP + ZN PP组24小时死亡率显著增加（P < 0.05）。CLP引起AST活性的显著增加，其随着HO抑制而进一步增加。CLP可诱导HO-1 mRNA的表达。CLP后的AST水平随着HO抑制而显著升高。HO-1功能似乎有助于在腹膜炎期间升高肝脏cGMP，并且可能是对感染的重要肝脏适应性反应。(C)北京：科学出版社.
The hemodynamic effects of sepsis have been attributed in part to increased nitric oxide (NO) production and activation of guanylate cyclase, resulting in increased cGMP and relaxation of vascular smooth muscle. Heme oxygenase-1 (HO-1), a heat shock protein, has been shown to increase intracellular cGMP levels by formation of carbon monoxide (CO). We hypothesized that HO may be an important mediator of the hepatic response to infection. Male Swiss Webster mice underwent standard cecal ligation and puncture (CLP, 18 gauge 2X) or sham operation, and received either normal saline (NS) or Zn protoporphyrin IX (ZN PP IX), a competitive HO inhibitor (n = 6-8/group). Hepatic tissue samples were collected at 3, 6, 12, and 24 hr from separate mice. Serum was collected at 3 and 24 hr. A semiquantitative reverse transcriptase polymerase chain reaction method was used to measure HO-1 mRNA levels. Hepatic cGMP levels were measured by ELISA, Groups were repeated (n = 10/group) to assess mortality. Serum was collected at 3 and 24 hr to measure serum aspartate aminotransferase (AST) levels. HO-1 mRNA expression increased significantly by 3 hr after CLP and with HO inhibition alone (P < 0.05 vs sham + NS). HO-1 mRNA remained elevated through 24 hr. CLP animals with HO inhibition showed a significant reduction of hepatic cGMP following CLP compared with CLP + saline at 24 hr (P < 0.05), Mortality was significantly increased in the CLP + ZN PP group at 24 hr (P < 0.05 CLP NS vs CLP ZN PP). CLP caused a marked increase in AST activity, which was increased further with HO inhibition. HO-1 mRNA expression was induced by CLP. AST levels following CLP were markedly increased with HO inhibition. HO-1 function appeared to contribute to elevation of hepatic cGMP during peritonitis and may be an important hepatic adaptive response to infection. (C) 1997 Academic Press.