Kaneko H, Yang H, Ohning G, Taché Y
Center for Ulcer Research and Education/Gastroenteric Biology Center, Veterans Affairs Wadsworth Medical Center, Los Angeles, California 90073.
Am J Physiol. 1995 Apr;268(4 Pt 1):G548-52. doi: 10.1152/ajpgi.1995.268.4.G548.
The gastroprotective effect of kainic acid microinjected into the raphe pallidus (Rpa) at a dose subthreshold to increase acid secretion was investigated in urethan-anesthetized rats. Kainic acid (25 pg/30 nl) microinjected into the Rpa inhibited by 65.8% gastric damage induced by intragastric ethanol (60%). No protection was observed when kainic acid was injected outside of the Rpa. The cytoprotective effect was completely abolished by thyrotropin-releasing hormone (TRH) antibody microinjected bilaterally (1.3 micrograms/site) into the dorsal motor nucleus of the vagus (DMN), indomethacin (5 mg/kg ip), and atropine (0.3 mg/kg sc). Microinjection of TRH antibody outside of the DMN or of control antibody into the DMN did not modify the protective action induced by kainic acid into the Rpa. The TRH antibody microinjected alone into the DMN did not alter the severity of the ethanol-induced gastric lesions. These data indicate that excitation of Rpa neurons by a low dose of kainic acid results in cytoprotection against ethanol lesions. Furthermore, this cytoprotection occurs as a result of TRH action in the DMN and activation of muscarinic and prostaglandin pathways.
在乌拉坦麻醉的大鼠中,研究了向中缝苍白核(Rpa)微量注射低于增加胃酸分泌阈值剂量的海藻酸的胃保护作用。向Rpa微量注射海藻酸(25 pg/30 nl)可使胃内乙醇(60%)诱导的胃损伤抑制65.8%。当海藻酸注射到Rpa以外的部位时,未观察到保护作用。双侧向迷走神经背运动核(DMN)微量注射促甲状腺激素释放激素(TRH)抗体(1.3微克/部位)、吲哚美辛(5毫克/千克,腹腔注射)和阿托品(0.3毫克/千克,皮下注射)可完全消除这种细胞保护作用。在DMN以外微量注射TRH抗体或向DMN注射对照抗体不会改变海藻酸向Rpa注射所诱导的保护作用。单独向DMN微量注射TRH抗体不会改变乙醇诱导的胃损伤的严重程度。这些数据表明,低剂量海藻酸对Rpa神经元的兴奋作用可导致对乙醇损伤的细胞保护。此外,这种细胞保护作用是由于TRH在DMN中的作用以及毒蕈碱和前列腺素途径的激活而产生的。