Delayed healing of gastric ulcers in adjuvant arthritis rats: Role of acid secretion and basic fibroblast growth factor

被引：7

作者：

Kato, S ^{[1
]}

Ogawa, Y ^{[1
]}

Tanaka, A ^{[1
]}

Kunikata, T ^{[1
]}

Takeuchi, K ^{[1
]}

机构：

[1] Kyoto Pharmaceut Univ, Dept Pharmacol & Expt Therapeut, Kyoto 6078414, Japan

来源：

DIGESTION | 2001年 / 63卷 / 03期

关键词：

adjuvant arthritis; healing of gastric ulcer; acid secretion; basic fibroblast growth factor;

D O I：

10.1159/000051886

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background/Aim: We examined the healing process of chronic gastric ulcers in adjuvant-induced arthritic rats and investigated the mechanism for delayed ulcer healing in arthritic rats, in relation to acid secretion and basic fibroblast growth factor (bFGF). Methods: Arthritis was induced in male dark Agouti rats by a single injection of Freund's complete adjuvant (FCA), while gastric ulcers were induced by thermal cauterization (70 degreesC for 30 s) 7 days after FCA injection. Results: Injection of FCA induced severe arthritis in all animals with a marked acid hypersecretion. The healing of gastric ulcers was significantly delayed in arthritic rats as compared with normal rats. Daily administration of indomethacin delayed ulcer healing in both normal and arthritic rats, but this effect was more pronounced in the latter. In contrast, the healing of gastric ulcers was significantly promoted in both normal and arthritic rats by omeprazole at a dose that inhibited acid secretion completely. The delayed healing of gastric ulcers was not influenced by twice daily administration of NG-nitro-L-arginine methyl ester, aminoguanidine or FR167653 (IL-1/TNF-alpha synthesis inhibitor), but was significantly accelerated by CS-23 (recombinant human bFGF) in a dose-dependent manner, without effect on the acid secretion. The expression of bFGF was markedly increased after ulceration, but this response was decreased in arthritic rats. Conclusion: The healing of gastric ulcers was delayed in arthritic rats, and this mechanism may be partly attributable to both acid hypersecretion and less expression of bFGF. Copyright (C) 2001 S. Karger AG, Basel.

引用

页码：171 / 179

页数：9

共 24 条

[11]

DiPasquale G., Welaj P., Ulcerogenic potential of indomethacin in arthritic and non-arthritic rats, J Pharm Pharmacol, 25, pp. 831-832, (1973)

[12]

Wang J.Y., Yamasaki S., Takeuchi K., Okabe S., Delayed healing of acetic acid-induced gastric ulcers in rats by indomethacin, Gastroenterology, 96, pp. 393-402, (1989)

[13]

Konturek S.J., Brzozowski T., Majka J., Pytko-Polonczyk J., Stachura J., Inhibition of nitric oxide synthase delays healing of chronic gastric ulcers, Eur J Pharmacol, 239, pp. 215-217, (1993)

[14]

Akiba Y., Nakamura M., Mori M., Suzuki H., Oda M., Kimura H., Miura S., Tsuchiya M., Ishii H., Inhibition of inducible nitric oxide synthase delays gastric ulcer healing in the rat, J Clin Gastroenterol, 27, 1 SUPPL., (1998)

[15]

Yamamoto N., Sakai F., Yamazaki H., Nakahara K., Okuhara M., Effect of FR167653, a cytokine suppressive agent, on endotoxin-induced disseminated intravascular coagulation, Eur J Pharmacol, 314, pp. 137-142, (1996)

[16]

Shimizu N., Watanabe T., Arakawa T., Fujiwara Y., Higuchi K., Kuroki T., Pentoxifylline accelerates gastric ulcer healing in rats: Roles of tumor necrosis factor alpha and neutrophils during the early phase of ulcer healing, Digestion, 61, pp. 157-164, (2000)

[17]

Takahashi S., Kobayashi N., Okabe S., Regulation by endogenous interleukin-1 of mRNA expression of healing-related factors in gastric ulcers in rats, J Pharmacol Exp Ther, 291, pp. 634-641, (1999)

[18]

Yamamoto O., Okada Y., Okabe S., Effects of a proton pump inhibitor, omeprazole, on gastric secretion and gastric and duodenal ulcers or erosions in rats, Dig Dis Sci, 29, pp. 394-401, (1984)

[19]

Inauen W., Wyss P.A., Kayser S., Baumgartner A., Schurer-Maly C.C., Koelz H.R., Halter F., Influence of prostaglandins, omeprazole, and indomethacin on healing of experimental gastric ulcers in the rat, Gastroenterology, 95, pp. 636-641, (1988)

[20]

Okabe S., Pfeiffer C.J., Chronicity of acetic acid ulcer in the rat stomach, Am J Dig Dis, 17, pp. 619-629, (1972)

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