Effects of Carbon Monoxide on Lipopolysaccharide Induced Rat Intestinal Tract Injury_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

1.Intensive Care Unit, The First Affiliated Hospital of Nanjing Medical University， Nanjing 210029, China;;
2.Department of Emergency, Huashan Hospital, Fudan University, Shanghai 200040, China;;
3.Department of Emergency, The Sixth Hospital Affiliated Shanghai Jiaotong University, Shanghai 200233, China;

Corresponding author：

Keywords：

Carbon monoxide,Intestinal tract,Injury,Mitogen-activated protein kinase

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

【 Abstract 】 Objective To investigate the effects of 250 ml/m3 carbon monoxide (CO) inhalation or intraperitoneal infusion on lipopolysaccharide (LPS) induced rat intestinal tract injury, and to detect the roles of p38 mitogen-activated protein kinase (MAPK) pathway during CO administration. Methods After received 5 mg/kg LPS or an equal volume of normal saline by intravenous injection, 108 male SD rats were randomly divided into 6 groups: control group, CO inhalation (250 ml/m3) group, CO intraperitoneal infusion (250 ml/m3 at a rate of 2 L/min) group, LPS (5 mg/kg) group, LPS (5 mg/kg)+CO inhalation (250 ml/m3) group and LPS (5 mg/kg)+CO intraperitoneal infusion (250 ml/m3 at a rate of 2 L/min) group. The animals were differently sacrificed at 1, 3 and 6 h for the observation, and the ileum tissues were homogenized for determination the levels of platelet activator factor (PAF), intercellular adhesion molecule-1 (ICAM-1) and interlukin-10 (IL-10) with enzyme-lined immunosorbent assay, the content of maleic dialdehyde (MDA) with thiobarbitric acid, the activity of myeloperoxidase (MPO) with chemical method, the activity of superoxide dismutase (SOD) with hydroxylamine, the activity of phosphorylated p38 MAPK with Western blot, the pathology with light microscope, and the extents of cell apoptosis were showed by the ratio of the apoptotic cells which had less DNA to the total cells of a cell-suspension sample by using the flow cytometry after being stained with propidium iodide. Results Compared with both control, CO inhalation and intraperitoneal infusion group at the same time point, the levels of PAF, ICAM-1, MDA, MPO, cell apoptosis rate and the phosphorylated p38 MAPK protein in LPS group were increased, while IL-10 and SOD were decreased (P ＜ 0.05 or 0.01), and accompanied by severe intestinal tract injury. There were no statistics differences at the different time point in the same group. PAF, ICAM-1, MDA, MPO and cell apoptosis rate in both LPS+CO inhalation group and LPS+CO intraperitoneal infusion group were lower, while IL-10 and SOD were higher than the corresponding value in LPS group at the same time point (all P ＜ 0.05), with ameliorate injury too, but the expression of phosphorylated p38 MAPK was further up-regulated than that of LPS group (all P ＜ 0.05). However, there were no significant differences in these parameters between LPS+CO inhalation group and LPS+CO intraperitoneal infusion group. Conclusion 250 ml/m3 CO inhalation and intraperitoneal infusion exerts the similar protection against LPS induced rat intestinal tract injury via anti-oxidant, anti-inflammation, and anti-apoptosis. This may involve the p38 MAPK pathway.

Citation： LIU Shaohua,MA Ke,XU Bing,XU Xinrong. Effects of Carbon Monoxide on Lipopolysaccharide Induced Rat Intestinal Tract Injury. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2008, 15(3): 174-179. doi: Copy

1.	刘少华, 马可, 许兵, 等. 一氧化碳吸入对内毒素诱导大鼠多器官损伤的影响及其机制 [J]. 中华实验外科杂志, 2006; 23（6）∶758.
2.	马可, 刘少华, 许兵, 等. 一氧化碳对内毒素血症肠道细胞凋亡的影响 [J]. 中华急诊医学杂志, 2006; 15（4）∶323.
3.	Chang L, Karin M. Mammalian MAP kinase signalling cascades [J]. Nature, 2001; 410(6824)∶37.
4.	Nakao A, Kimizuka K, Stolz DB, et al. Carbon monoxide inhalation protects rat intestinal grafts from ischemia/reperfusion injury [J]. Am J Pathol, 2003; 163(4)∶1587.
5.	Brouard S, Otterbein LE, Anrather J, et al. Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis [J]. J Exp Med, 2000; 192(7)∶1015.
6.	孙敬平, 马洪升. 应激状态下肠屏障功能的变化及其机理的研究进展 [J]. 中国普外基础与临床杂志, 2005; 12（3）∶314.
7.	Gibbons SJ, Farrugia G. The role of carbon monoxide in the gastrointestinal tract [J]. J Physiol, 2004; 556(Pt 2)∶325.
8.	Zuckerbraun BS, McCloskey CA, Gallo D, et al. Carbon monoxide prevents multiple organ injury in a model of hemorrhagic shock and resuscitation [J]. Shock, 2005; 23(6)∶527.
9.	Morisaki H, Katayama T, Kotake Y, et al. Roles of carbon monoxide in leukocyte and platelet dynamics in rat mesenteric during sevoflurane anesthesia [J]. Anesthesiology, 2001; 95(1)∶192.
10.	Morisaki H, Katayama T, Kotake Y, et al. Carbon monoxide modulates endotoxin-induced microvascular leukocyte adhesion through platelet-dependent mechanisms [J]. Anesthesiology, 2002; 97(3)∶701.
11.	闫文生, 阚文宏, 黄巧冰, 等. 脂多糖诱导小鼠肠组织ICAM-1表达的变化及p38 MAPK在其中的作用 [J]. 中国病理生理杂志, 2002; 18（5）∶701.
12.	Otterbein LE, Bach FH, Alam J, et al. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway [J]. Nat Med, 2000; 6(4)∶422.
13.	王祖耀, 胡廷泽, 韦福康, 等. 白介素10 在腹腔感染和早期脓毒血症对阻止炎性细胞因子释放作用的实验研究 [J]. 中国普外基础与临床杂志， 2000; 7（5）∶291.
14.	Moore BA, Otterbein LE, Türler A, et al. Inhaled carbon monoxide suppresses the development of postoperative ileus in the murine small intestine [J]. Gastroenterology, 2003; 124(2)∶377.
15.	Moore BA, Otterbein LE, Türler A, et al. Opposite effect of oxidative stress on inducible nitric oxide synthase and haem oxygenase-1 expression in intestinal inflammation: anti-inflammatory effect of carbon monoxide [J]. J Pathol, 2004; 204(3)∶296.
16.	Wang X, Wang Y, Kim HP, et al. Carbon monoxide protects against hyperoxia-induced endothelial cell apoptosis by inhibiting reactive oxygen species formation [J]. J Biol Chem, 2007; 282(3)∶1718.
17.	Mayr FB, Spiel A, Leitner J, et al. Effects of carbon monoxide inhalation during experimental endotoxemia in humans [J]. Am J Respir Crit Care Med, 2005; 171(4)∶354.
18.	Wagener FA, Volk HD, Willis D, et al. Different faces of the heme-heme oxygenase system in inflammation [J]. Pharmacol Rev, 2003; 55(3)∶551.
19.	Otterbein LE, Otterbein SL, Ifedigbo E, et al. MKK3 mitogen-activated protein kinase pathway mediates carbon monoxide-induced protection against oxidant-induced lung injury [J]. Am J Pathol, 2003; 163(6)∶2555.
20.	Reunanen N, Li SP, Ahonen M, et al. Activation of p38 alpha MAPK enhances collagenase-1 matrix metalloproteinase (MMP)-1 and stromelysin-1 (MMP-3) expression by mRNA stabilization [J]. J Biol Chem, 2002; 277(35)∶32360.
21.	Zhang X, Shan P, Alam J, et al. Carbon monoxide modulates Fas/Fas ligand, caspases, and Bcl-2 family proteins via the p38alpha mitogen-activated protein kinase pathway during ischemia-reperfusion lung injury [J]. J Biol Chem, 2003; 278(24)∶22061.
22.	Zhang X, Shan P, Otterbein LE, et al. Carbon monoxide inhibition of apoptosis during ischemia-reperfusion lung injury is dependent on the p38 mitogen-activated protein kinase pathway and involves caspase 3 [J]. J Biol Chem, 2003; 278(2)∶1248.
23.	Zhang X, Shan P, Alam J, et al. Carbon monoxide differentially modulates STAT1 and STAT3 and inhibits apoptosis via a phosphatidylinositol 3-kinase/Akt and p38 kinase-dependent STAT3 pathway during anoxia-reoxygenation injury [J]. J Biol Chem, 2005; 280(10)∶8714.
24.	Kohmoto J, Nakao A, Stolz DB, et al. Carbon monoxide protects rat lung transplants from ischemia-reperfusion injury via a mechanism involving p38 MAPK pathway [J]. Am J Transplant, 2007; 7(10)∶2279.

1. 刘少华, 马可, 许兵, 等. 一氧化碳吸入对内毒素诱导大鼠多器官损伤的影响及其机制 [J]. 中华实验外科杂志, 2006; 23（6）∶758.
2. 马可, 刘少华, 许兵, 等. 一氧化碳对内毒素血症肠道细胞凋亡的影响 [J]. 中华急诊医学杂志, 2006; 15（4）∶323.
3. Chang L, Karin M. Mammalian MAP kinase signalling cascades [J]. Nature, 2001; 410(6824)∶37.
4. Nakao A, Kimizuka K, Stolz DB, et al. Carbon monoxide inhalation protects rat intestinal grafts from ischemia/reperfusion injury [J]. Am J Pathol, 2003; 163(4)∶1587.
5. Brouard S, Otterbein LE, Anrather J, et al. Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis [J]. J Exp Med, 2000; 192(7)∶1015.
6. 孙敬平, 马洪升. 应激状态下肠屏障功能的变化及其机理的研究进展 [J]. 中国普外基础与临床杂志, 2005; 12（3）∶314.
7. Gibbons SJ, Farrugia G. The role of carbon monoxide in the gastrointestinal tract [J]. J Physiol, 2004; 556(Pt 2)∶325.
8. Zuckerbraun BS, McCloskey CA, Gallo D, et al. Carbon monoxide prevents multiple organ injury in a model of hemorrhagic shock and resuscitation [J]. Shock, 2005; 23(6)∶527.
9. Morisaki H, Katayama T, Kotake Y, et al. Roles of carbon monoxide in leukocyte and platelet dynamics in rat mesenteric during sevoflurane anesthesia [J]. Anesthesiology, 2001; 95(1)∶192.
10. Morisaki H, Katayama T, Kotake Y, et al. Carbon monoxide modulates endotoxin-induced microvascular leukocyte adhesion through platelet-dependent mechanisms [J]. Anesthesiology, 2002; 97(3)∶701.
11. 闫文生, 阚文宏, 黄巧冰, 等. 脂多糖诱导小鼠肠组织ICAM-1表达的变化及p38 MAPK在其中的作用 [J]. 中国病理生理杂志, 2002; 18（5）∶701.
12. Otterbein LE, Bach FH, Alam J, et al. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway [J]. Nat Med, 2000; 6(4)∶422.
13. 王祖耀, 胡廷泽, 韦福康, 等. 白介素10 在腹腔感染和早期脓毒血症对阻止炎性细胞因子释放作用的实验研究 [J]. 中国普外基础与临床杂志， 2000; 7（5）∶291.
14. Moore BA, Otterbein LE, Türler A, et al. Inhaled carbon monoxide suppresses the development of postoperative ileus in the murine small intestine [J]. Gastroenterology, 2003; 124(2)∶377.
15. Moore BA, Otterbein LE, Türler A, et al. Opposite effect of oxidative stress on inducible nitric oxide synthase and haem oxygenase-1 expression in intestinal inflammation: anti-inflammatory effect of carbon monoxide [J]. J Pathol, 2004; 204(3)∶296.
16. Wang X, Wang Y, Kim HP, et al. Carbon monoxide protects against hyperoxia-induced endothelial cell apoptosis by inhibiting reactive oxygen species formation [J]. J Biol Chem, 2007; 282(3)∶1718.
17. Mayr FB, Spiel A, Leitner J, et al. Effects of carbon monoxide inhalation during experimental endotoxemia in humans [J]. Am J Respir Crit Care Med, 2005; 171(4)∶354.
18. Wagener FA, Volk HD, Willis D, et al. Different faces of the heme-heme oxygenase system in inflammation [J]. Pharmacol Rev, 2003; 55(3)∶551.
19. Otterbein LE, Otterbein SL, Ifedigbo E, et al. MKK3 mitogen-activated protein kinase pathway mediates carbon monoxide-induced protection against oxidant-induced lung injury [J]. Am J Pathol, 2003; 163(6)∶2555.
20. Reunanen N, Li SP, Ahonen M, et al. Activation of p38 alpha MAPK enhances collagenase-1 matrix metalloproteinase (MMP)-1 and stromelysin-1 (MMP-3) expression by mRNA stabilization [J]. J Biol Chem, 2002; 277(35)∶32360.
21. Zhang X, Shan P, Alam J, et al. Carbon monoxide modulates Fas/Fas ligand, caspases, and Bcl-2 family proteins via the p38alpha mitogen-activated protein kinase pathway during ischemia-reperfusion lung injury [J]. J Biol Chem, 2003; 278(24)∶22061.
22. Zhang X, Shan P, Otterbein LE, et al. Carbon monoxide inhibition of apoptosis during ischemia-reperfusion lung injury is dependent on the p38 mitogen-activated protein kinase pathway and involves caspase 3 [J]. J Biol Chem, 2003; 278(2)∶1248.
23. Zhang X, Shan P, Alam J, et al. Carbon monoxide differentially modulates STAT1 and STAT3 and inhibits apoptosis via a phosphatidylinositol 3-kinase/Akt and p38 kinase-dependent STAT3 pathway during anoxia-reoxygenation injury [J]. J Biol Chem, 2005; 280(10)∶8714.
24. Kohmoto J, Nakao A, Stolz DB, et al. Carbon monoxide protects rat lung transplants from ischemia-reperfusion injury via a mechanism involving p38 MAPK pathway [J]. Am J Transplant, 2007; 7(10)∶2279.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effects of Carbon Monoxide on Lipopolysaccharide Induced Rat Intestinal Tract Injury

Abstract Full text Figures/Tables Video References Cited by

Format

Content