Role of Cyclooxygenase-2 for Fluid Secretion by the Inflamed Gallbladder Mucosa

被引：19

作者：

Nilsson B. ^{[1
]}

Delbro D. ^{[1
]}

Hedin L. ^{[1
]}

Friman S. ^{[1
]}

Andius S. ^{[1
]}

Svanvik J. ^{[1
]}

机构：

[1] Institute for Surgical Sciences, Sahlgrenska University Hospital

来源：

Journal of Gastrointestinal Surgery | 1998年 / 2卷 / 3期

关键词：

Cholecystitis; Cystic Duct; Vasoactive Intestinal Peptide; Fluid Secretion; Chronic Cholecystitis;

D O I：

10.1016/S1091-255X(98)80022-X

中图分类号：

学科分类号：

摘要：

Inflammatory fluid secretion by the gallbladder mucosa in experimental cholecystitis is induced by activation of cyclooxygenase, which leads to an increase in prostaglandin formation. Cyclooxygenase exists as a constitutive (cyclooxygenase-1) and an inducible (cyclooxygenase-2) isoform. The aim of this study was to demonstrate the role of cyclooxygenase-2 in inflammatory fluid secretion of the feline gallbladder. Experiments were performed 10 weeks after a surgical procedure in which chronic cholecystitis was induced in cats by ligation of the cystic duct and implantation of a gallstone in the gallbladder. Gallbladder fluid transport was continuously monitored via a perfusion system. In inflamed gallbladders the continuous fluid secretion was reversed to absorption by intravenous injection of the selective cyclooxygenase-2 blocker, NS 398 (P <0.001). Increased levels of the inducible cyclooxygenase-2 were shown by immunoblotting in inflamed gallbladders. Selective pharmacologic blockade of cyclooxygenase-2 reduced the prostaglandin E2 release to the inflamed gallbladder lumen (P <0.01). These data suggest that cyclooxygenase-2 is involved in the inflammatory response during chronic cholecystitis. Selective cyclooxygenase-2 blockers may offer an alternative to traditional nonsteroidal anti-inflammatory drugs with fewer side effects in patients with cholecystitis who are awaiting operation.

引用

页码：269 / 277

页数：8

共 30 条

[1]

Jivegard L., Thornell E., Svanvik J., Fluid secretion by the gallbladder mucosa in experimental cholecystitis is influenced by intramural nerves, Dig Dis Sci, 32, pp. 1389-1394, (1987)

[2]

Thornell E., Jivegard L., Bukhave K., Rask-Madsen J., Svanvik J., Prostaglandin E<sub>2</sub> formation by the gallbladder in experimental cholecystitis, Gut, 27, pp. 370-373, (1986)

[3]

Nilsson B., Delbro D., Hedin L., Conradi N., Thune A., Friman S., Wennmalm A., Yan Z., Svanvik J., Role of nitric oxide in induction of inflammatory fluid secretion by the mucosa of the feline gallbladder, Gastroenterology, 110, pp. 598-606, (1996)

[4]

Vane J.R., Botting R.M., New insights into the mode of action of antiinflammatory drugs, Inflamm Res, 44, pp. 1-10, (1995)

[5]

Feng L., Xia Y., Garcia G.E., Hwang D., Wilson C.B., Involvement of reactive oxygen intermediates in cyclooxygenase-2 expression induced by interleukin-1, tumor necrosis factor-α, and lipopolysaccharide, J Clin Invest, 95, pp. 1669-1675, (1995)

[6]

Mitchell J.A., Akarasereenont P., Thiemermann C., Flower R.J., Vane J.R., Selectivity of nonsteroidal anti-inflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase, Proc Natl Acad Sci USA, 90, pp. 11693-11697, (1994)

[7]

Vane J.R., Botting R.M., Mechanism of action of antiinflammatory drugs, Scand J Rheumatol Suppl, 102, pp. 9-21, (1996)

[8]

Svanvik J., Thornell E., Zettergren L., Gallbladder function in experimental cholecystitis: Reversal of the inflammatory net fluid "secretion" into the gallbladder by indomethacin, Surgery, 89, pp. 500-506, (1981)

[9]

Parnham M.J., Inflammation 93, Drug News Perspect, 6, pp. 737-742, (1994)

[10]

Jivegard L., Thornell E., Bjork S., Svanvik J., The effects of morphine and enkephalins on gallbladder function in experimental cholecystitis. Inhibition of inflammatory gallbladder secretion, Scand J Gastroenterol, 20, pp. 1049-1056, (1985)

← 1 2 3 →