Departamento de Farmacología y Fisiología, Unidad de Fisiología, Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, Spain.
Neurogastroenterol Motil. 2010 May;22(5):564-72, e123. doi: 10.1111/j.1365-2982.2009.01439.x. Epub 2009 Dec 9.
Lipopolysaccharide (LPS) decreases intestinal contractility and induces the release of reactive oxygen species, which play an important role in the pathogenesis of sepsis. p38 mitogen-activated protein kinase (MAPK) can be activated by a variety of stimuli such as LPS. The aims of this study were: (i) to investigate the role of p38 MAPK in the effect of LPS on (a) the acetylcholine, prostaglandin E(2) and KCl-induced contractions of rabbit duodenum and (b) the oxidative stress status; (ii) to localize the active form of p38 in the intestine.
Rabbits were injected with (i) saline, (ii) LPS, (iii) SB203580, a specific p38 MAPK inhibitor or (iv) SB203580 + LPS. Duodenal contractility was studied in an organ bath. SB203580 was also tested in vitro. The protein expression of p-p38 and total p38 was measured by Western blot and p-p38 was localized by immunohistochemistry. The formation of products of oxidative damage to proteins (carbonyls) and lipids (MDA+4-HDA) was quantified in intestine and plasma.
ACh, PGE(2) and KCl-induced contractions decreased with LPS. LPS increased phospho-p38 expression and the levels of carbonyls and MDA+4-HDA. SB203580 blocked the effect of LPS on the ACh, PGE(2) and KCl-induced contractions in vivo and in vitro and the levels of carbonyls and MDA+4-HDA. P-p38 was detected in neurons of the myenteric plexus and smooth muscle cells of duodenum.
CONCLUSIONS & INFERENCES: Lipopolysaccharide decreases the duodenal contractility in rabbits and increases the production of free radicals. p38 MAPK is a mediator of these effects.
脂多糖 (LPS) 可降低肠道收缩性并诱导活性氧物质的释放，而活性氧物质在败血症的发病机制中起着重要作用。p38 丝裂原活化蛋白激酶 (MAPK) 可被 LPS 等多种刺激激活。本研究的目的是：(i) 研究 p38 MAPK 在 LPS 对（a）兔十二指肠乙酰胆碱、前列腺素 E2 (PGE2) 和 KCl 诱导收缩的作用，以及（b）氧化应激状态的作用；(ii) 定位 p38 在肠道中的活性形式。
兔子被注射了(i) 生理盐水、(ii) LPS、(iii) SB203580，一种特定的 p38 MAPK 抑制剂，或 (iv) SB203580+LPS。在器官浴中研究十二指肠收缩性。SB203580 也在体外进行了测试。通过 Western blot 测定 p-p38 和总 p38 的蛋白表达，并用免疫组化定位 p-p38。定量测定肠道和血浆中蛋白质（羰基）和脂质（MDA+4-HDA）氧化损伤产物的形成。
LPS 降低了 ACh、PGE2 和 KCl 诱导的收缩。LPS 增加了磷酸化 p38 的表达以及羰基和 MDA+4-HDA 的水平。SB203580 阻断了 LPS 在体内和体外对 ACh、PGE2 和 KCl 诱导的收缩以及羰基和 MDA+4-HDA 水平的影响。p-p38 被检测到在肌间神经丛的神经元和十二指肠平滑肌细胞中。
脂多糖降低了兔子的十二指肠收缩性并增加了自由基的产生。p38 MAPK 是这些作用的介导物。
