PATHOPHYSIOLOGY OF LPS-INDUCED GASTROINTESTINAL INJURY IN THE RAT: ROLE OF SECRETORY PHOSPHOLIPASE A2
PATHOPHYSIOLOGY OF LPS-INDUCED GASTROINTESTINAL INJURY IN THE RAT: ROLE OF SECRETORY PHOSPHOLIPASE A2
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LPS 引起的大鼠胃肠损伤的病理生理学：分泌性磷脂酶 A2 的作用
DOI：
10.1097/shk.0b013e318160f47f
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发表时间：
2007
期刊：
影响因子：
3.1
通讯作者：
E. Dial
中科院分区：
文献类型：
--
作者：
Mayssa Zayat;L. Lichtenberger;E. Dial
磷脂酰胆碱（PC）疏水层覆盖并保护胃肠道（GI）表面，有助于屏障的完整性。在脓毒症等危重疾病中，肠道屏障的完整性受到损害，这可能与PC的降解有关。本研究旨在探讨分泌型磷脂酶A2 （sPLA2）在lps诱导的GI损伤中的作用。采用LPS （5 mg/kg）或生理盐水处理大鼠0.5、1、3和5 h，收集胃和回肠腔内含量，测定sPLA2活性，并用薄层色谱法分析腔内脂质，测定溶索- pc含量。用异硫氰酸荧光素葡聚糖4000在体内评估GI的通透性，并在使用或不使用特定sPLA2抑制剂的情况下对大鼠进行测试。LPS在5 h时诱导胃和回肠腔sPLA2活性和溶索- pc含量显著增加。此外，LPS处理大鼠在5 h时胃和回肠对异硫氰酸荧光素葡聚糖的GI通透性显著增加，用sPLA2抑制剂预处理可以阻止这一现象。在LPS的作用下，sPLA2在胃肠道腔内的活性增加，降解细胞外保护性磷脂层和膜，产生有害的溶酶pc和增加胃肠道通透性。口服活性sPLA2抑制剂预处理可阻断lps诱导的胃肠道通透性增加，这可能为创伤和其他患者强化胃肠道粘膜屏障和预防内毒素并发症提供了一种新途径。
A hydrophobic layer of phosphatidylcholine (PC) overlies and protects the surface of the gastrointestinal (GI) tract, contributing to barrier integrity. During critical illness such as sepsis, gut barrier integrity is compromised, which could be related to degradation of PC. The purpose of this study was to investigate a role for luminal (secretory) phospholipase A2 (sPLA2) in LPS-induced GI injury. Rats were treated with LPS (5 mg/kg) or saline for 0.5, 1, 3, and 5 h. The gastric and ileal luminal contents were collected for determination of sPLA2 activity, and the luminal lipids were analyzed using thin layer chromatography for lyso-PC content. The GI permeability was assessed in vivo with fluorescein-isothiocyanate dextran 4000 and rats were tested with or without a specific sPLA2 inhibitor. LPS induced significant increases in sPLA2 activity and lyso-PC content in the gastric and ileal lumens at 5 h. In addition, LPS treated rats showed a significant increase in GI permeability to fluorescein-isothiocyanate dextran in both the stomach and ileum at 5 h, which was prevented by pretreatment with the sPLA2 inhibitor. In response to LPS, sPLA2 activity increases in the GI tract lumen where it may degrade the extracellular protective phospholipid layer and membranes, producing injurious lyso-PC and increased GI permeability. Pretreatment with an orally active sPLA2 inhibitor blocks the LPS-induced increase in GI permeability, and may suggest a new approach to fortify the GI mucosal barrier and prevent complications from endotoxin in trauma and other patients.
幽门螺杆菌的磷脂酶活性及其对铋盐的抑制作用。
影响因子：
3.1
作者：
Ottlecz,A;Romero,JJ;Hazell,SL;Graham,DY;Lichtenberger,LM
通讯作者：
Lichtenberger,LM
改善肠道干细胞的获取，作为肠道基因转移的一步。
影响因子：
4.2
作者：
Sandberg,JW;Lau,C;Jacomino,M;Finegold,M;Henning,SJ
通讯作者：
Henning,SJ