Effect of polaprezinc on impaired healing of chronic gastric ulcers in adjuvant-induced arthritic rats--role of insulin-like growth factors (IGF)-1.
Effect of polaprezinc on impaired healing of chronic gastric ulcers in adjuvant-induced arthritic rats--role of insulin-like growth factors (IGF)-1.
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波拉普锌对佐剂诱发关节炎大鼠慢性胃溃疡愈合受损的影响——胰岛素样生长因子 (IGF)-1 的作用。
DOI：
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发表时间：
2001
期刊：
影响因子：
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通讯作者：
K. Takeuchi
中科院分区：
文献类型：
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作者：
S. Kato;A. Tanaka;Y. Ogawa;K. Kanatsu;K. Seto;Tomoyuki Yoneda;K. Takeuchi
Polaprezinc，N-（3-aminopropionyl）-L-histidinatozinc，已显示刺激间充质细胞中胰岛素样生长因子-1（IGF-1）的产生，该多肽在胃上皮创伤修复中起作用。本研究旨在检查Polaprezinc对促炎剂诱导的关节炎大鼠慢性胃溃疡愈合受损的影响，与IGF-1相关。通过单次注射弗氏完全佐剂（FCA）在雄性黑琼脂（DA）大鼠中诱导关节炎，并在FCA注射后7天通过热烧灼（70 ℃，30秒）诱导胃溃疡。口服给予奥美拉唑（30 mg/kg）。每日一次，而重组人IGF-1（rhIGF-1）（30微克/kg，s.c.）或泊普瑞锌（3-10 mg/kg，p.o.）每天给药两次，从溃疡后3天开始，共14天。在溃疡形成后第10天和第17天，与正常大鼠相比，关节炎大鼠胃溃疡的愈合显著延迟。IGF-1 mRNA的表达在溃疡粘膜中明显增加，但这种反应在关节炎大鼠中明显减弱。重复给予聚普瑞锌以剂量依赖性方式加速正常和关节炎大鼠胃溃疡的愈合，并且这种作用在关节炎大鼠中更加明显。同样，奥美拉唑治疗也显著促进了正常和关节炎大鼠胃溃疡的愈合。另一方面，rhIGF-1能显著促进关节炎大鼠胃溃疡的愈合，而对正常大鼠胃溃疡的愈合无明显影响。这些结果表明，关节炎大鼠慢性胃溃疡的愈合受损，至少部分是由于IGF-1的表达减少，和polaprezinc改善关节炎大鼠胃溃疡的延迟愈合，可能是通过增加IGF-1的生产。
Polaprezinc, N-(3-aminopropionyl)-L-histidinatozinc, has been shown to stimulate the production of insulin-like growth factor-1 (IGF-1) in mesenchymal cells, the polypeptide playing a role in the gastric epithelial wound repair. The present study was performed to examine the effect of polaprezinc on the impaired healing of chronic gastric ulcers in adjuvant-induced arthritic rats, in relation to IGF-1. Arthritis was induced in male Dark Agouti (DA) rats by a single injection of Freund's complete adjuvant (FCA), and the gastric ulcers were induced by thermal cauterization (70 degrees C for 30 sec) 7 days after FCA injection. Omeprazole (30 mg/kg) was administered p.o. once daily, while recombinant human IGF-1 (rhIGF-1) (30 micrograms/kg, s.c.) or polaprezinc (3-10 mg/kg, p.o.) was administered twice daily, starting from 3 days after ulceration for 14 days. The healing of gastric ulcers was significantly delayed in arthritic rats as compared to normal rats on day 10 and 17 following ulceration. The expression of IGF-1 mRNA was markedly increased in the ulcerated mucosa, but this response was apparently attenuated in arthritic rats. Repeated administration of polaprezinc accelerated the healing of gastric ulcers in both normal and arthritic rats, in a dose-dependent manner, and this effect was more pronounced in arthritic rats. Likewise, treatment with omeprazole also significantly promoted the healing of gastric ulcers in both normal and arthritic rats. On the other hand, rhIGF-1 significantly promoted the gastric ulcer healing in arthritic rats without any effect on that in normal rats. These results suggest that the impaired healing of chronic gastric ulcers in arthritic rats is, at least partly, accounted for by less expression of IGF-1, and the polaprezinc improves the delayed healing of gastric ulcers in arthritic rats, probably through an increase in IGF-1 production.