胰淀素对大鼠胃溃疡中枢保护作用的相关机制研究。

Investigation on the mechanisms involved in the central protective effect of amylin on gastric ulcers in rats.

作者信息

Guidobono F, Pagani F, Ticozzi C, Sibilia V, Netti C

机构信息

Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Italy.

出版信息

Br J Pharmacol. 1998 Sep;125(1):23-8. doi: 10.1038/sj.bjp.0702029.

DOI:10.1038/sj.bjp.0702029

PMID:9776339

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1565590/

Abstract

The mechanisms involved in the protective effect of amylin (administered into the brain ventricle, i.c.v.) on gastric ulcers induced by the oral administration of ethanol 50% (EtOH, 2 ml/rat) or indomethacin (indomethacin, 20 mg kg(-1), at a dosing volume of 5 ml) were investigated in rats. 2. The possible involvement of endogenous nitric oxide (NO) in the beneficial effect of amylin against EtOH-induced ulcers was examined. The inhibitor of NO-synthesis, NG-nitro-L-arginine methyl ester (L-NAME, 70 mg kg(-1), s.c.) was injected 30 min before amylin (2.2 microg/rat, i.c.v.) followed by EtOH after a further 30 min. Rats were sacrificed 1 h after EtOH. L-NAME completely removed the protective effect of amylin. 3. The interaction between amylin and gastric nonprotein sulfhydryl groups was studied. The rats were treated with N-ethyl-maleimide (NEM, 25 mg kg(-1), s.c.) 30 min before amylin (2.2 microg/rat, i.c.v.) followed by EtOH 30 min after or by indomethacin 5 min after amylin. Rats were sacrificed 1 h or 6 h respectively after EtOH or indomethacin. NEM counteracted the protective effect of amylin against EtOH-induced ulcers but not against those provoked by indomethacin. 4. To determine whether amylin was able to promote ulcer healing, the peptide was injected 5 min after EtOH or 1 h after indomethacin. In the case of EtOH, the beneficial effect of amylin was lost whereas it was still effective on indomethacin-induced ulcers. 5. The results indicate that: the mechanisms involved in the antiulcer effects of amylin are different in these two types of gastric lesions probably because of the different etiopathology of various types of ulcers. Endogenous NO and nonprotein sulfhydryl groups are involved in the mucosal protective effects of amylin on EtOH and not on indomethacin-induced ulcers. Furthermore the effectiveness of amylin against indomethacin-induced lesions when administered after the ulcerogenic process has started suggests that amylin is involved not only in the protection but also in the healing mechanisms in this type of ulcer.

摘要

研究了胰淀素（经脑室注射，i.c.v.）对经口给予50%乙醇（EtOH，2 ml/大鼠）或吲哚美辛（吲哚美辛，20 mg kg⁻¹，给药体积5 ml）诱导的大鼠胃溃疡的保护作用机制。2. 研究了内源性一氧化氮（NO）在胰淀素对乙醇诱导溃疡的有益作用中可能的参与情况。在胰淀素（2.2 μg/大鼠，i.c.v.）注射前30分钟皮下注射一氧化氮合成抑制剂NG-硝基-L-精氨酸甲酯（L-NAME，70 mg kg⁻¹），再过30分钟后给予乙醇。乙醇给药1小时后处死大鼠。L-NAME完全消除了胰淀素的保护作用。3. 研究了胰淀素与胃非蛋白巯基之间的相互作用。在胰淀素（2.2 μg/大鼠，i.c.v.）注射前30分钟皮下给予N-乙基马来酰亚胺（NEM，25 mg kg⁻¹），30分钟后给予乙醇或胰淀素注射5分钟后给予吲哚美辛。乙醇或吲哚美辛给药后1小时或6小时分别处死大鼠。NEM抵消了胰淀素对乙醇诱导溃疡的保护作用，但对吲哚美辛诱导的溃疡无效。4. 为了确定胰淀素是否能够促进溃疡愈合，在乙醇给药后5分钟或吲哚美辛给药后1小时注射该肽。对于乙醇诱导的溃疡，胰淀素的有益作用消失，而对吲哚美辛诱导的溃疡仍有效。5. 结果表明：胰淀素在这两种类型的胃部病变中的抗溃疡作用机制可能不同，这可能是由于不同类型溃疡的病因病理不同。内源性NO和非蛋白巯基参与了胰淀素对乙醇诱导溃疡的黏膜保护作用，而对吲哚美辛诱导的溃疡无效。此外，在致溃疡过程开始后给予胰淀素对吲哚美辛诱导病变的有效性表明，胰淀素不仅参与了这种类型溃疡的保护机制，还参与了愈合机制。