Nagahashi Shoichi, Suzuki Hidekazu, Miyazawa Masaharu, Nagata Hiroshi, Suzuki Masayuki, Miura Soichiro, Ishii Hiromasa
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Free Radic Biol Med. 2002 Oct 15;33(8):1073-81. doi: 10.1016/s0891-5849(02)00998-x.
The relationship between Helicobacter pylori colonization and the formation of stress-induced gastric mucosal injury remains unknown. Since ammonia (NH(3)) is known as one of the injurious factors in H. pylori-colonized gastric mucosa, the present study is designed to investigate the level of stress-induced gastric mucosal oxidative injury with or without intragastric NH(3) overloading. To apply emotional stress, the communication box paradigm was used in the mouse model. Mice (C57BL/6, male) were pretreated with distilled water (responder-H(2)O) or 0.01% NH(3) (responder-NH(3)) through a gastric tube once a day for a week. Emotional stress was then applied to the responder mice for 3 h per day for 3 d by watching and hearing the behavior of the sender mice subjected to electric shocks to the feet (2 mA, 10 s, 50 s interval). After the communication box protocol, the tissue MPO activity, the contents of TBA-reactive substances (TBARS), and the level of gastric mucosal HSP70 were examined. Responder-NH(3) mice developed more severe gastric lesions than the responder-H(2)O subjects. MPO activity and TBARS contents were enhanced significantly in the responder-NH(3) group compared with the responder-H(2)O subjects. Although the contents of HSP70 in the gastric mucosa increased in the responder-H(2)O group compared with the control-H(2)O animals, they were significantly attenuated in the responder-NH(3) mice. Excess intragastric NH(3) was able to enhance the formation of emotional stress-induced gastric mucosal lesions. This injury may be associated with the enhanced production of oxygen free radicals from accumulated neutrophils under the NH(3)-mediated cancellation of gastric mucosal cytoprotective HSP70.
幽门螺杆菌定植与应激性胃黏膜损伤形成之间的关系尚不清楚。由于氨（NH₃）被认为是幽门螺杆菌定植的胃黏膜中的损伤因素之一，本研究旨在调查在有或无胃内氨超载情况下应激性胃黏膜氧化损伤的程度。为了施加情绪应激，在小鼠模型中使用了通讯箱范式。小鼠（C57BL/6，雄性）每天通过胃管给予蒸馏水（反应组-H₂O）或0.01%氨（反应组-NH₃）预处理，持续一周。然后通过观察和聆听接受足部电击（2 mA，10 s，间隔50 s）的发送组小鼠的行为，对反应组小鼠每天施加3小时情绪应激，持续3天。在通讯箱实验方案后，检测组织髓过氧化物酶（MPO）活性、硫代巴比妥酸反应性物质（TBARS）含量以及胃黏膜热休克蛋白70（HSP70）水平。反应组-NH₃小鼠比反应组-H₂O小鼠出现更严重的胃部病变。与反应组-H₂O小鼠相比，反应组-NH₃组的MPO活性和TBARS含量显著增强。虽然与对照-H₂O动物相比，反应组-H₂O组胃黏膜中HSP70含量增加，但在反应组-NH₃小鼠中显著减弱。胃内氨过量能够增强情绪应激诱导的胃黏膜病变的形成。这种损伤可能与在氨介导的胃黏膜细胞保护HSP70消除作用下，积聚的中性粒细胞产生的氧自由基增加有关。
