褪黑素给药对大鼠体内乙醇诱导的胃十二指肠损伤的抑制作用。

Suppressive effect of melatonin administration on ethanol-induced gastroduodenal injury in rats in vivo.

作者信息

Melchiorri D, Sewerynek E, Reiter R J, Ortiz G G, Poeggeler B, Nisticò G

机构信息

Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio 78284-7762, USA.

出版信息

Br J Pharmacol. 1997 May;121(2):264-70. doi: 10.1038/sj.bjp.0701104.

DOI:10.1038/sj.bjp.0701104

PMID:9154336

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1564668/

Abstract

Melatonin protection against ethanol-induced gastroduodenal injury was investigated in duodenumligated rats. 2. Melatonin, injected i.p. 30 min before administration of 1 ml of absolute ethanol, given by gavage, significantly decreased ethanol-induced macroscopic, histological and biochemical changes in the gastroduodenal mucosa. 3. Ethanol-induced lesions were detectable as haemorrhagic streaks. Ethanol administration damaged 36% and 25% of the total gastric and duodenal surface, respectively. Melatonin treatment reduced ethanol-induced gastric and duodenal damage to 14% and 8%, respectively. When indomethacin was given together with ethanol, the gastric damaged area was 44% of the total surface, while the duodenal damaged area was 35%; melatonin administration reduced the damage to only 13% of the total gastric surface and to 12% of total duodenal surface. 4. Both stomach and duodenum of ethanol-treated animals showed polymorphonuclear leukocyte (PMN) infiltration. The number of PMN increased more than 600 and 200 times in stomach and duodenum, respectively, following ethanol administration. Melatonin treatment reduced ethanol-induced PMN infiltration by 38% in the stomach and 20% in the duodenum. In indomethacin-ethanol-treated rats, the number of PMN increased by 875% compared to control group in the stomach and by 264% in duodenum. Melatonin administration reduced the indomethacin-ethanol-induced PMN rise by 57% in the stomach and 40% in the duodenum. 5. Gastroduodenal total glutathione (tGSH) concentration and glutathione reductase (GSSG-Rd) activity were significantly reduced following ethanol and indomethacin-ethanol administration. Melatonin ameliorated both the decrease in tGSH concentration as well as the reduction of GSSG-Rd activity elicited by ethanol both in the stomach and duodenum; melatonin was effective against indomethacin-ethanol-induced damage only in the stomach. 6. Ethanol-induced gastroduodenal damage is believed to be mediated by the generation of free radicals. Recently, a number of in vivo and in vitro experiments have shown melatonin to be an effective antioxidant and free radical scavenger; thus, we conclude that the protection by melatonin against ethanol-induced gastroduodenal injury is due, at least in part, to its radical scavenging activity.

摘要

在十二指肠结扎大鼠中研究了褪黑素对乙醇诱导的胃十二指肠损伤的保护作用。2. 在通过灌胃给予1毫升无水乙醇前30分钟腹腔注射褪黑素，可显著减轻乙醇诱导的胃十二指肠黏膜的宏观、组织学和生化变化。3. 乙醇诱导的损伤表现为出血条纹。给予乙醇后，分别损伤了胃和十二指肠总表面积的36%和25%。褪黑素治疗将乙醇诱导的胃和十二指肠损伤分别降至14%和8%。当吲哚美辛与乙醇同时给予时，胃损伤面积占总表面积的44%，而十二指肠损伤面积为35%；给予褪黑素后，胃损伤面积仅降至总表面积的13%，十二指肠损伤面积降至总表面积的12%。4. 乙醇处理动物的胃和十二指肠均出现多形核白细胞（PMN）浸润。给予乙醇后，胃和十二指肠中PMN的数量分别增加了600倍和200倍以上。褪黑素治疗使乙醇诱导的胃中PMN浸润减少38%，十二指肠中减少20%。在吲哚美辛 - 乙醇处理的大鼠中，胃中PMN的数量比对照组增加了875%，十二指肠中增加了264%。给予褪黑素使吲哚美辛 - 乙醇诱导的胃中PMN升高减少57%，十二指肠中减少40%。5. 给予乙醇和吲哚美辛 - 乙醇后，胃十二指肠总谷胱甘肽（tGSH）浓度和谷胱甘肽还原酶（GSSG - Rd）活性显著降低。褪黑素改善了乙醇引起的胃和十二指肠中tGSH浓度的降低以及GSSG - Rd活性的降低；褪黑素仅对吲哚美辛 - 乙醇诱导的胃损伤有效。6. 乙醇诱导的胃十二指肠损伤被认为是由自由基的产生介导的。最近，许多体内和体外实验表明褪黑素是一种有效的抗氧化剂和自由基清除剂；因此，我们得出结论，褪黑素对乙醇诱导的胃十二指肠损伤的保护作用至少部分归因于其自由基清除活性。