Matsumoto Y, Kanamoto K, Kawakubo K, Aomi H, Matsumoto T, Ibayashi S, Fujishima M
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
Am J Physiol Gastrointest Liver Physiol. 2001 May;280(5):G897-903. doi: 10.1152/ajpgi.2001.280.5.G897.
Epidermal growth factor (EGF) has been shown to exert gastric hyperemic and gastroprotective effects via capsaicin-sensitive afferent neurons, including the release of calcitonin gene-related peptide (CGRP). We examined the protective and vasodilatory effects of EGF on the gastric mucosa and its interaction with sensory nerves, CGRP, and nitric oxide (NO) in anesthetized rats. Intragastric EGF (10 or 30 microg) significantly reduced gastric mucosal lesions induced by intragastric 60% ethanol (50.6% by 10 microg EGF and 70.0% by 30 microg EGF). The protective effect of EGF was significantly inhibited by pretreatment with capsaicin desensitization, human CGRP1 antagonist hCGRP-(8-37), or N(omega)-nitro-L-arginine methyl ester (L-NAME). Intravital microscopy showed that topically applied EGF (10-1,000 microg/ml) dilated the gastric mucosal arterioles dose dependently and that this vasodilatory effect was significantly inhibited by equivalent pretreatments. These findings suggest that EGF plays a protective role against ethanol-induced gastric mucosal injury, possibly by dilating the gastric mucosal arterioles via capsaicin-sensitive afferent neurons involving CGRP and NO mechanisms.
表皮生长因子（EGF）已被证明可通过辣椒素敏感传入神经元发挥胃充血和胃保护作用，包括释放降钙素基因相关肽（CGRP）。我们研究了EGF对麻醉大鼠胃黏膜的保护和血管舒张作用及其与感觉神经、CGRP和一氧化氮（NO）的相互作用。胃内给予EGF（10或30微克）可显著减轻胃内60%乙醇诱导的胃黏膜损伤（10微克EGF减轻50.6%，30微克EGF减轻70.0%）。辣椒素脱敏预处理、人CGRP1拮抗剂hCGRP-(8-37)或N(ω)-硝基-L-精氨酸甲酯（L-NAME）可显著抑制EGF的保护作用。活体显微镜检查显示，局部应用EGF（10 - 1000微克/毫升）可剂量依赖性地扩张胃黏膜小动脉，且同等预处理可显著抑制这种血管舒张作用。这些发现表明，EGF可能通过辣椒素敏感传入神经元，涉及CGRP和NO机制，扩张胃黏膜小动脉，从而对乙醇诱导的胃黏膜损伤发挥保护作用。
