Sphingosine-1-Phosphate Attenuates Lung Injury Induced by Intestinal Ischemia/Reperfusion in Mice: Role of Inducible Nitric-Oxide Synthase

被引：0
作者：
Renyu Ding
Jiali Han
Yu Tian
Renxuan Guo
Xiaochun Ma
机构：
[1] The First Affiliated Hospital of China Medical University,Department of Intensive Care Unit
[2] The First Affiliated Hospital of China Medical University,Department of Otolaryngology
[3] The First Affiliated Hospital of China Medical University,Department of General Surgery
来源：
Inflammation | 2012年 / 35卷
关键词：
acute lung injury; ischemia/reperfusion; reperfusion injury; sphingosine-1-phosphate; nitric-oxide synthase;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Multiple organ failure, including acute lung injury (ALI), is a common complication of intestinal ischemia/reperfusion (I/R) injuries and contributes to its high mortality rate. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that enhances vascular barrier function and has anti-inflammatory effects. In the current study, we investigated the effect of S1P on lung injury induced by intestinal I/R. Mice were randomly assigned to one of the following groups: (1) sham-operated mice, (2) mice exposed to superior mesenteric artery occlusion for 45 min followed by reperfusion for 6 h, or (3) mice exposed to I/R that received S1P (100 μg/kg, administered by peritoneal injection). S1P markedly attenuated lung injury, manifested by the improvement of histological changes and significant decreases of lung water content. Moreover, S1P markedly reduced MDA levels and MPO activity in the lung tissues, and plasma levels of proinflammatory cytokines. In addition, S1P treatment significantly suppressed NO generation accompanied by down-regulation of iNOS expression. The results indicate that S1P has a protective effect on lung injury induced by I/R, which may be related to its suppression of iNOS-induced NO generation. S1P seems to be an effective therapeutic agent for intestinal I/R-related lung injury.
引用
收藏
页码：158 / 166
页数：8
相关论文
共 293 条
[1]  
Homer-Vanniasinkam S(1997)Post-ischaemic organ dysfunction: a review Eur. J. Vasc. Endovasc. Surg. 14 195-203
[2]  
Crinnion JN(2003)Future research directions in acute lung injury: summary of a National Heart, Lung, and Blood Institute working group Am. J. Respir. Crit. Care Med. 167 1027-1035
[3]  
Gough MJ(1999)Nonadrenergic noncholinergic vasodilation of guinea pig pulmonary arteries is mediated by nitric oxide Can. J. Physiol. Pharmacol. 77 89-95
[4]  
Matthay MA(1996)Nonadrenergic noncholinergic relaxation of human pulmonary arteries is partially mediated by nitric oxide Am. J. Respir. Crit. Care Med. 154 629-632
[5]  
Zimmerman GA(2002)Cell-specific nitric oxide synthase-isoenzyme expression and regulation in response to endotoxin in intact rat lungs Lab. Invest. 82 425-441
[6]  
Esmon C(1994)Inducible nitric oxide synthase is increased in murine lung epithelial cells by cytokine stimulation Biochem. Biophys. Res. Commun. 198 835-843
[7]  
Bhattacharya J(1992)Cytokines and lipopolysaccharide induce nitric oxide synthase in cultured rat pulmonary artery smooth muscle Am. J. Respir. Cell Mol. Biol. 7 471-476
[8]  
Coller B(2005)Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network Nat. Rev. Immunol. 5 560-570
[9]  
Doerschuk CM(2004)Cell surface receptors in lysophospholipid signaling Semin. Cell Dev. Biol. 15 457-465
[10]  
Floros J(2004)Physiological and pathological actions of sphingosine 1-phosphate Semin. Cell Dev. Biol. 15 513-520
12345678910