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Novokinin inhibits gastric acid secretion and protects against alcohol-induced gastric injury in rats

机译:诺科宁抑制胃酸分泌并防止大鼠醇诱导的胃损伤

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Novokinin (Arg-Pro-Leu-Lys-Pro-Trp), a potent vasorelaxing and hypotensive peptide modified from ovokinin, exhibits highly selective affinity for the AT(2) receptor. However, its role in gastrointestinal functions is still not fully understood. In this study, we found that novokinin inhibited basal gastric acid secretion and protected gastric mucosa from alcohol-induced injury in a dose-related manner in rats after intracerebroventricular (i.c.v.) administration. Novokinin significantly decreased basal gastric acid output at the dose of 50 and 100 nmol/rat. The effect of novokinin on gastric acid secretion was reversed by central injection of PD 123319 (10 nmol/rat), an AT2 receptor antagonist, and peripheral injection of indomethacin (10 mg/kg), an inhibitor of prostaglandin synthesis. Meanwhile, pre-treatment with novokinin at doses of 10, 50, and 100 nmol/rat significantly reduced the alcohol-induced gastric mucosal injury compared to the ulcer-control group, which was inhibited by indomethacin (10 mg/kg). The result showed a remarkable increase in the level of prostaglandin E2 (PGE(2)), glutathione (GSH), and a decrease in malondialdehyde (MDA) after i.c.v. administration of novokinin. These findings suggest that the inhibitory effect of novokinin on gastric acid secretion is probably mediated via an AT(2) receptor-prostaglandins (PGs) pathway. The gastroprotective effect of novokinin might be attributed to the inhibition of acid secretion, the cytoprotection of PGs, and the antioxidant property. (C) 2016 Elsevier Inc. All rights reserved.
机译:Novokinin(Arg-Pro-Leu-Lys-Pro-TRP),从Ovokinin修饰的有效的血管肠化和低血压肽,对(2)受体具有高度选择性的亲和力。然而,它在胃肠功能中的作用仍然没有完全理解。在这项研究中,我们发现诺科宁蛋白在大鼠脑内(I.C.V.)给药后,在大鼠中,诺科宁抑制基础胃酸分泌和受醇诱导的损伤的保护胃粘膜。诺科宁在50和100nmol /大鼠的剂量下显着降低了基础胃酸输出。通过中央注射Pd 123319(10nmol /大鼠),AT2受体拮抗剂和外周注射吲哚美辛(10mg / kg),诺喹啉素对胃酸分泌的影响是反转的,使吲哚美辛(10mg / kg),前列腺素合成的抑制剂。同时,与10,50和100nmol /大鼠剂量的诺肝素的预处理显着降低了与溃疡对照组相比的醇诱导的胃粘膜损伤,其被吲哚美辛(10mg / kg)抑制。结果表明,前列腺素E2(PGE(2)),谷胱甘肽(GSH)的水平显着增加,以及在I.C.V之后的丙二醛(MDA)的降低。诺科宁毒素施用。这些发现表明,诺科宁蛋白对胃酸分泌的抑制作用可能通过AT(2)受体 - 前列腺素(PGS)途径介导。诺糖素的胃保护作用可能归因于抑制酸分泌,PGS的细胞保护和抗氧化剂性能。 (c)2016年Elsevier Inc.保留所有权利。

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