Mechano-transcription of COX-2 is a common response to lumen dilation of the rat gastrointestinal tract.
Mechano-transcription of COX-2 is a common response to lumen dilation of the rat gastrointestinal tract.
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DOI：
10.1111/j.1365-2982.2012.01918.x
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发表时间：
2012-07
影响因子：
3.5
通讯作者：
Shi XZ
中科院分区：
文献类型：
--
作者：
Lin YM;Li F;Shi XZ
在贲门失弛缓症、幽门狭窄和肠梗阻等梗阻性肠疾病中，受影响节段的管腔明显扩张，运动功能明显受损。我们验证了一个假设，即管腔扩张中的机械应力导致整个胃肠道平滑肌中环氧化酶-2 （COX-2）的诱导，导致运动功能障碍。在大鼠食管下括约肌（LES）、幽门括约肌和回肠上施加梗阻带（12 × 3 mm） 48小时，诱导管腔扩张。用远端结肠的球囊扩张来模拟体内的机械拉伸。在体外组织培养系统中模拟直接拉伸食管、胃底和回肠的肌肉条。部分梗阻在LES、幽门和回肠显著增加COX-2 mRNA和蛋白在扩张段口腔外肌层的表达，但在肠外肌层没有。在体内直接拉伸管腔或在体外直接拉伸肌条可显著诱导COX-2的表达。球囊扩张节段的平滑肌收缩力明显受到抑制。然而，用COX-2抑制剂NS-398治疗可恢复收缩力。此外，胃出口梗阻患者体内给予NS-398可显著改善胃排空。通过阻断或直接扩张对肠腔进行机械扩张可诱导COX-2基因在整个胃肠道中的表达。机械应力诱导的COX-2在管腔扩张条件下有助于运动功能障碍。
In obstructive bowel disorders (OBDs) such as achalasia, pyloric stenosis, and bowel obstruction, the lumen of the affected segments is markedly dilated and the motility function is significantly impaired. We tested the hypothesis that mechanical stress in lumen dilation leads to induction of cyclo-oxygenase-2 (COX-2) in smooth muscle throughout the gastrointestinal (GI) tract, contributing to motility dysfunction. Lumen dilation was induced in vivo with obstruction bands (12 × 3 mm) applied over the lower esophageal sphincter (LES), the pyloric sphincter, and the ileum in rats for 48 hr. Mechanical stretch in vivo was also emulated by balloon distension of the distal colon. Direct stretch of muscle strips from the esophagus, gastric fundus, and ileum was mimicked in an in vitro tissue culture system. Partial obstruction in the LES, pylorus, and ileum significantly increased expression of COX-2 mRNA and protein in the muscularis externae of the dilated segment oral to the occlusions, but not in the aboral segment. Direct stretch of the lumen in vivo or of muscle strips in vitro markedly induced COX-2 expression. The smooth muscle contractility was significantly suppressed in the balloon distended segments. However, treatment with COX-2 inhibitor NS-398 restored the contractility. Furthermore, in vivo administration of NS-398 in gastric outlet obstruction significantly improved gastric emptying. Mechanical dilation of the gut lumen by occlusion or direct distension induces gene expression of COX-2 throughout the GI tract. Mechanical stress-induced COX-2 contributes to motility dysfunction in conditions with lumen dilation.
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影响因子：
2.9
作者：
Mönnikes, H;Rüter, J;Tebbe, JJ
通讯作者：
Tebbe, JJ
影响因子：
24.5
作者：
MEIJSSEN, MAC;TILANUS, HW;ONG, GL
通讯作者：
ONG, GL
影响因子：
9
作者：
Naef, Markus;Mouton, Wolfgang G.;Wagner, Hans E.
通讯作者：
Wagner, Hans E.
影响因子：
2.9
作者：
Korswagen, Lindy-Anne;Schrama, Jolanda G.;Hunfeld, Michiel A. J. M.
通讯作者：
Hunfeld, Michiel A. J. M.
影响因子：
--
作者：
PRIHODA, M;FLATT, A;SUMMERS, RW
通讯作者：
SUMMERS, RW