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缺血和环氧化酶抑制剂氟尼辛对脂多糖经马空肠体外转运的影响。

Effects of ischemia and the cyclooxygenase inhibitor flunixin on in vitro passage of lipopolysaccharide across equine jejunum.

作者信息

Tomlinson Julia E, Blikslager Anthony T

机构信息

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.

出版信息

Am J Vet Res. 2004 Oct;65(10):1377-83. doi: 10.2460/ajvr.2004.65.1377.

DOI:10.2460/ajvr.2004.65.1377
PMID:15524324
Abstract

OBJECTIVE

To determine whether ischemia and flunixin affect in vitro lipopolysaccharide (LPS) absorption in samples of the jejunum of horses.

ANIMALS

12 horses.

PROCEDURE

Horses were anesthetized, a midline celiotomy was performed, and the jejunum was located. Two 30-cm sections of jejunum (60 cm apart) were selected. One segment was designated as control tissue; ischemia was induced in the other segment for 120 minutes. Horses were then euthanatized. Mucosa from each jejunal segment was mounted on Ussing chambers and treated with or without flunixin. Tissues from 6 horses were used to assess permeability to radiolabeled LPS; mucosal samples from the remaining 6 horses were incubated with fluorescent-labeled LPS (FITC-LPS) and examined histologically. Production of tumor necrosis factor-alpha (TNF-alpha) and production of LPS-binding protein (LBP) were assessed as indicators of mucosal response to LPS.

RESULTS

Ischemia significantly increased mucosal permeability to LPS, but by 180 minutes, the mucosa was not more permeable than control tissue. Flunixin treatment adversely affected intestinal barrier function throughout the experiment but did not result in increased mucosal permeability to LPS. Compared with control tissues, LBP production was increased by ischemia and reduced by exposure to LPS. In ischemic tissue, FITC-LPS entered the lamina propria but TNF-alpha was produced on the mucosal side only, indicating little response to the absorbed LPS.

CONCLUSIONS AND CLINICAL RELEVANCE

Ischemia increased LPS passage across equine jejunal mucosa. Flunixin delayed mucosal recovery but did not exacerbate LPS absorption. Evaluation of the clinical importance of flunixin-associated delayed mucosal recovery requires further in vivo investigation.

摘要

目的

确定局部缺血和氟尼辛是否会影响马空肠样本中脂多糖(LPS)的体外吸收。

动物

12匹马。

步骤

对马实施麻醉,进行中线剖腹术并找到空肠。选取两段30厘米长的空肠(相距60厘米)。一段指定为对照组织;另一段诱导局部缺血120分钟。然后对马实施安乐死。将每个空肠段的黏膜安装在尤斯灌流小室上,并分别给予或不给予氟尼辛处理。用6匹马的组织评估对放射性标记LPS的通透性;其余6匹马的黏膜样本与荧光标记LPS(FITC-LPS)一起孵育并进行组织学检查。评估肿瘤坏死因子-α(TNF-α)的产生和LPS结合蛋白(LBP)的产生,作为黏膜对LPS反应的指标。

结果

局部缺血显著增加了黏膜对LPS的通透性,但到180分钟时,该黏膜的通透性并不比对照组织更高。在整个实验过程中,氟尼辛处理对肠道屏障功能产生不利影响,但并未导致黏膜对LPS的通透性增加。与对照组织相比,LBP的产生因局部缺血而增加,因暴露于LPS而减少。在缺血组织中,FITC-LPS进入固有层,但TNF-α仅在黏膜侧产生,表明对吸收的LPS反应很小。

结论及临床意义

局部缺血增加了LPS穿过马空肠黏膜的通透性。氟尼辛延迟了黏膜恢复,但并未加剧LPS吸收。评估氟尼辛相关的黏膜恢复延迟的临床重要性需要进一步的体内研究。

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