Comparative protection against rat intestinal reperfusion injury by a new inhibitor of sPLA2, COX-1 and COX-2 selective inhibitors, and an LTC4 receptor antagonist
Comparative protection against rat intestinal reperfusion injury by a new inhibitor of sPLA2, COX-1 and COX-2 selective inhibitors, and an LTC4 receptor antagonist
复制标题
DOI：
10.1038/sj.bjp.0705402
复制
发表时间：
2003-09-01
影响因子：
7.3
通讯作者：
Taylor, SM
中科院分区：
文献类型：
--
作者：
Arumugam, TV;Arnold, N;Taylor, SM
1比较新的IIa Spla(2)组抑制剂与选择性COX-1、COX-2和LTC4拮抗剂对大鼠小肠缺血再灌注(I/R)后局部和远端组织损伤的影响。2在没有抑制剂的急性缺血(30min)和再灌注(150min)损伤模型中，出现明显的肠出血、水肿和粘膜损伤，中性粒细胞减少，血清天冬氨酸氨基转移酶(AST)水平升高和降压。3缺血前应用Spla(2)抑制剂(Ila组)，静脉注射5 mg(kg-1)。或10 mg kg(-1)灌胃。显著抑制I/R引起的中性粒细胞减少、血清AST水平升高、肠水肿和降压。4环氧合酶-2抑制剂Celebrex(10 mg kg(-1)i.v.)LTC4拮抗剂扎鲁司特(1 mg kg(-1)i.v.)对I/R诱导的AST、水肿和中性粒细胞减少也有明显改善。低血压只被LTC4拮抗剂降低。COX-1抑制剂氟尼辛(1 mg kg(-1)i.v.)5大鼠I/R损伤的组织学检查显示，与未用药组相比，所有药物对粘膜层损伤均有一定的保护作用。静脉注射Spla(2)抑制剂比COX-1或COX-2抑制剂更有效地预防大鼠I/R损伤。6这些结果表明，Spla(2)的新抑制剂(Ila组)对口服或静脉注射后的大鼠小肠I/R损伤具有保护作用。COX-2和LTC4抑制剂对肠I/R损伤也有一定的保护作用。我们的研究提示SplA(2)(Ila组)可能在大鼠肠I/R中起致病作用。
1 A new group IIa sPLA(2) inhibitor was compared with selective inhibitors of COX-1, COX-2 and an LTC4 antagonist for effects on local and remote tissue injuries following ischaemia and reperfusion (I/R) of the small intestine in rats.2 In an acute model of ischaemia (30 min) and reperfusion (150 min) injury in the absence of inhibitors, there was significant intestinal haemorrhage, oedema and mucosal damage, neutropenia, elevated serum levels of aspartate aminotransferase (AST) and hypotension.3 Preischaemic treatment with the inhibitor of sPLA(2) (Group Ila), at 5 mg kg(-1) i.v. or 10 mg kg(-1) p.o. significantly inhibited I/R-induced neutropenia, the elevation of serum levels of AST, intestinal oedema and hypotension.4 Pretreatment with the COX-2 inhibitor celebrex (10 mg kg(-1) i.v.) and the LTC4 antagonist zafirlukast (1 mg kg(-1) i.v.) also showed marked improvement with I/R-induced AST, oedema and neutropenia. Hypotension was only reduced by the LTC4 antagonist. The COX-1 inhibitor flunixin (1 mg kg(-1) i.v.) did not effect improvement in the markers of tissue injury.5 Histological examination of rat I/R injury showed that all of the drugs offered some protection to the mucosal layer damage compared to no drug treatment. Given i.v., the sPLA(2) inhibitor was more effective than either the COX-1 or COX-2 inhibitors in preventing rat I/R injury.6 These results indicate that a potent new inhibitor of sPLA(2) (group Ila) protects the rat small intestine from I/R injury after oral or intravenous administration. COX-2 and LTC4 inhibitors also showed some beneficial effects against intestinal I/R injury. Our study suggests that sPLA(2) (Group Ila) may have a pathogenic role in intestinal I/R in rats.