Fukumura D, Kurose I, Miura S, Serizawa H, Sekizuka E, Nagata H, Tsuchiya M, Ishii H
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
J Gastroenterol Hepatol. 1996 Mar;11(3):279-85. doi: 10.1111/j.1440-1746.1996.tb00076.x.
The aim of the present study was to clarify the involvement of endogenous endothelin in the pathogenesis of gastric mucosal damage. The rat stomach was exposed and repeated electrical stimulation (RES) was applied to the small arterial wall close to the lesser curvature. Significant mucosal haemorrhagic lesions (ulcer and erosion) were noted within 30 min after RES. Intravital microscopic observations revealed that an arteriolar constriction occurred in the submucosal layer of the rat stomach approximately 5 min after the completion of RES. Following the arteriolar constriction, the mucosal blood flow of the rat stomach, which was monitored by using a laser Doppler velocimeter, decreased to approximately 30% of the control value. The plasma immunoreactive endothelin-1 level in the regional blood of the stomach was significantly increased immediately after RES preceding the decrease in mucosal blood flow. Immunohistochemical studies revealed that endothelin-1 and big-endothelin-1 were detectable in the arteriolar endothelium around the muscularis mucosa, supporting the involvement of endothelin-1 in RES-induced mucosal ischaemia. In addition, BQ-123, a specific antagonist of the endothelin A (ETA) receptor, attenuated the reduction of blood flow and the development of haemorrhagic lesions observed in gastric mucosa subjected to RES. The results of the present study suggest that an excessive production of endothelin-1 in the arteriolar endothelium leads to microvascular derangements accompanied by haemorrhagic alterations of the gastric mucosa.
本研究的目的是阐明内源性内皮素在胃黏膜损伤发病机制中的作用。暴露大鼠胃，对靠近胃小弯的小动脉壁进行重复电刺激（RES）。RES后30分钟内可见明显的黏膜出血性病变（溃疡和糜烂）。活体显微镜观察显示，RES结束后约5分钟，大鼠胃黏膜下层的小动脉出现收缩。小动脉收缩后，用激光多普勒血流仪监测的大鼠胃黏膜血流量降至对照值的约30%。胃局部血液中的血浆免疫反应性内皮素-1水平在黏膜血流量下降之前的RES后立即显著升高。免疫组织化学研究显示，在黏膜肌层周围的小动脉内皮中可检测到内皮素-1和大内皮素-1，支持内皮素-1参与RES诱导的黏膜缺血。此外，内皮素A（ETA）受体的特异性拮抗剂BQ-123减轻了RES处理的胃黏膜中观察到的血流量减少和出血性病变的发展。本研究结果表明，小动脉内皮中内皮素-1的过度产生导致微血管紊乱，并伴有胃黏膜的出血性改变。
