Tanaka S, Taché Y, Kaneko H, Guth P H, Kaunitz J D
West Los Angeles Veterans Administration Medical Center, CURE: Digestive Diseases Research Center, Department of Medicine, California, USA.
Gastroenterology. 1997 Feb;112(2):409-17. doi: 10.1053/gast.1997.v112.pm9024294.
BACKGROUND & AIMS: Central vagal stimulation induced by the thyrotropin-releasing hormone analogue RX 77368 injected intracisternally in urethane-anesthetized rats is gastroprotective. In an in vivo system, the effects of central RX 77368 on discrete components of the rat gastric mucosal barrier were studied to determine if these effects were prostaglandin synthesis dependent.
Using intravital microscopy, intracellular pH of gastric surface cells, mucus gel thickness, gastric mucosal blood flow, and acid output were measured simultaneously in vivo.
Intracisternal RX 77368 significantly increased acid output, gel thickness, and blood flow. Indomethacin enhanced the RX 77368-induced increase in acid output but had no effect on measures of gastric defense during mucosal superfusion with neutral solutions. During acid superfusion, RX 77368 delayed acidification and enhanced recovery of surface cell intracellular pH. These latter effects were reversed partially by indomethacin. Omeprazole abolished RX 77368-induced acid secretion but did not alter its effects on gastric defense mechanisms.
In response to central vagal stimulation with RX 77368, gastric defense mechanisms were enhanced through prostaglandin-dependent and -independent pathways, in contrast to the prostaglandin-independent effects of intravenous pentagastrin. RX 77368-induced enhancements of gastric defense mechanisms did not occur as a result of acid secretion.
在氨基甲酸乙酯麻醉的大鼠中,脑池内注射促甲状腺激素释放激素类似物RX 77368所诱导的中枢迷走神经刺激具有胃保护作用。在一个体内系统中,研究了中枢性RX 77368对大鼠胃黏膜屏障离散成分的影响,以确定这些影响是否依赖于前列腺素合成。
使用活体显微镜在体内同时测量胃表面细胞的细胞内pH值、黏液凝胶厚度、胃黏膜血流量和酸分泌量。
脑池内注射RX 77368可显著增加酸分泌量、凝胶厚度和血流量。吲哚美辛增强了RX 77368诱导的酸分泌增加,但在黏膜用中性溶液灌注期间对胃防御指标无影响。在酸灌注期间,RX 77368延迟了酸化并增强了表面细胞内pH值的恢复。吲哚美辛部分逆转了这些后期效应。奥美拉唑消除了RX 77368诱导的酸分泌,但未改变其对胃防御机制的影响。
与静脉注射五肽胃泌素的不依赖前列腺素的作用相反,对RX 77368引起的中枢迷走神经刺激的反应中,胃防御机制通过依赖前列腺素和不依赖前列腺素的途径得到增强。RX 77368诱导的胃防御机制增强并非酸分泌所致。