Pihl L, Nylander O
Department of Neuroscience, Division of Physiology, Biomedical Center, Uppsala University, Uppsala, Sweden.
Acta Physiol (Oxf). 2006 Apr;186(4):279-90. doi: 10.1111/j.1748-1716.2006.01559.x.
Abdominal surgery evokes powerful biological responses that affect gastrointestinal functions. Here we investigate the role of the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoforms in post-operative duodenal ileus.
Proximal duodenum of anesthetized rats was perfused in situ with isotonic or hypotonic (50 mM) NaCl. Mucosal bicarbonate secretion, motility, mucosal permeability and effluent osmolality were determined in the absence and presence of different COX inhibitors.
The majority of control animals had no or few duodenal contractions and bicarbonate secretion averaged 10.9 +/- 1.4 micromol cm(-1) h(-1). These 'paralytic' controls responded to hypotonic NaCl with a small increase in mucosal permeability. In control animals exhibiting spontaneous duodenal contractions, the bicarbonate secretion was 50% higher and the hypotonicity-induced net increase in mucosal permeability sevenfold higher than in 'paralytic' controls. Treatment with the selective COX-2 inhibitors rofecoxib or parecoxib induced duodenal motility, increased bicarbonate secretion and potentiated the hypotonicity-induced increase in mucosal permeability. COX-2-inhibited animals had a twofold greater capacity to adjust luminal osmolality than 'paralytic' controls. The selective COX-1 inhibitor SC-560 only transiently stimulated motility and bicarbonate secretion and the hypotonicity-induced increase in mucosal permeability was smaller than in COX-2-inhibited animals.
Abdominal surgery increases the synthesis of prostanoids, particularly via the COX-2 isoform. This compromises the ability of the duodenum to contract and to secrete HCO and to adjust luminal osmolality possibly via altered mucosal permeability. It is proposed that studies of gastrointestinal functions in animals subjected to abdominal surgery should include animals pre-treated with a COX-2 inhibitor.
腹部手术会引发影响胃肠功能的强烈生物学反应。在此，我们研究环氧化酶 -1（COX -1）和环氧化酶 -2（COX -2）同工型在术后十二指肠麻痹中的作用。
对麻醉大鼠的近端十二指肠进行原位灌注等渗或低渗（50 mM）氯化钠溶液。在存在和不存在不同COX抑制剂的情况下，测定黏膜碳酸氢盐分泌、运动性、黏膜通透性和流出液渗透压。
大多数对照动物无十二指肠收缩或仅有少量收缩，碳酸氢盐分泌平均为10.9±1.4微摩尔/厘米⁻¹·小时⁻¹。这些“麻痹性”对照动物对低渗氯化钠溶液的反应是黏膜通透性略有增加。在表现出自发性十二指肠收缩的对照动物中，碳酸氢盐分泌高出50%，低渗引起的黏膜通透性净增加比“麻痹性”对照动物高7倍。用选择性COX -2抑制剂罗非昔布或帕罗昔布治疗可诱导十二指肠运动性，增加碳酸氢盐分泌，并增强低渗引起的黏膜通透性增加。COX -2抑制的动物调节管腔渗透压的能力比“麻痹性”对照动物大两倍。选择性COX -1抑制剂SC -560仅短暂刺激运动性和碳酸氢盐分泌，低渗引起的黏膜通透性增加比COX -2抑制的动物小。
腹部手术会增加前列腺素的合成，特别是通过COX -2同工型。这可能通过改变黏膜通透性损害十二指肠的收缩、分泌HCO以及调节管腔渗透压的能力。建议在接受腹部手术的动物中进行胃肠功能研究时应包括预先用COX -2抑制剂治疗的动物。
