Adaptive cytoprotection mediated by generated PGs (PGE_2 and/or PGI_2) through the release of CGRP.

通过释放 CGRP 产生的 PG（PGE_2 和/或 PGI_2）介导的适应性细胞保护。

• 批准号: 11672274
• 负责人: OHNO Takashi
• 金额: $ 1.47万
• 依托单位: KITASATO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672274/
• 关键词: Adaptive Cytoprotection; CGRP; Ethanol-Induced Gastric Mucosal Injury; PGE_2; PGI_2; Knockout Mice; Gastric Mucosal Microcirculation

A mechanism of adaptive cytoprotection believed to be related to production of endogenous prostaglandins (PGs). We tested whether PGs generated by mild irritant prevented gastric mucosal injury through the release of CGRP from the sensory nerves.Assessment of gross lesion in the stomach and Measurement of intragastric levels of CGRP and PGsPreperfusion with mildly hypertonic saline (1M Nacl) increased the generation of gastric PGE_2 and PGI_2, and reduced ethanol-induced mucosal damage. Exposure of ethanol after 1M NaCl increased intragastric CGRP levels and the protective action of 1M NaCl was inhibited by indomethacin and CGRP receptor antagonist, CGRP-(8-37). Intragastric perfusion of 50% ethanol after administration of PGI_2, but not of PGE_2, increased CGRP levels. Application of 1M NaCl to IP receptor-knockout mice (IPKO) did not elicit the protective effects seen in the wild type on ethanol-induced lesions. Protective effect of 1M NaCl was seen in EP3 receptor-knockout mice (EP3 … More KO) and wild-type counterparts. CGRP levels during ethanol perfusion was not increased in IPKO, but was increased in EP3KO and wild type counterparts after preperfusion of 1M NaCl.Gastric mucosal microcirculationThe 50% ethanol-induced constriction of venules (including collecting venules) that is cause of ethanol-induced gastric injury was inhibited by preapplication of 1M Nail. This preventive effect of 1M NaCl was inhibited by CGRP (8-37) or indomethacin. Preapplication of either PGE_2 or PGI_2 analog, which dose did not dilate gastric mucosal vessels directly, completely inhibited constrictions of venules induced by ethanol. This preventive effect of PGI_2 analog was abolished by CGRP (8-37), and the constriction of venules appeared again. That of PGE_2 was not abolished by CGRP (8-37).ConclusionsThese results indicate that the endogenous PGI_2 generated by 1M NaCl may have protective roles in gastric mucosal injury through enhancement of CGRP release from the gastric mucosa and that the endogenous PGE_2 generated may have protective roles through another mechanism. Less

适应性细胞保护的机制被认为与内源性前列腺素（pg）的产生有关。我们检测轻度刺激产生的PGs是否通过感觉神经释放CGRP来预防胃粘膜损伤。轻度高渗盐水（1M Nacl）再灌注可增加胃PGE_2和PGI_2的生成，减轻乙醇引起的粘膜损伤。经1M NaCl处理后的乙醇增加了胃内CGRP水平，吲哚美辛和CGRP受体拮抗剂CGRP-抑制了1M NaCl的保护作用（8-37）。PGI_2灌胃后灌胃50%乙醇可使CGRP水平升高，而PGE_2灌胃后不升高。将1M NaCl应用于IP受体敲除小鼠（IPKO），对乙醇诱导的病变没有产生野生型小鼠所见的保护作用。1M NaCl对EP3受体敲除小鼠（EP3…More KO）和野生型小鼠均有保护作用。乙醇灌注时IPKO的CGRP水平没有升高，但预灌注1M NaCl后EP3KO和野生型CGRP水平升高。胃粘膜微循环：预涂1M钉可抑制50%乙醇致胃损伤的小静脉（包括集静脉）收缩。CGRP（8-37）和吲哚美辛抑制了1M NaCl的这种预防作用。预应用PGE_2或PGI_2类似物，其剂量不直接扩张胃粘膜血管，完全抑制乙醇引起的小静脉收缩。PGI_2类似物的这种预防作用被CGRP所消除（8-37），小静脉收缩再次出现。CGRP对PGE_2的影响不明显（8-37）。结论1M NaCl产生的内源性PGI_2可能通过促进胃黏膜CGRP的释放对胃粘膜损伤具有保护作用，其产生的内源性PGE_2可能通过其他机制发挥保护作用。少

项目成果

K.Boku, et al: "Possible preventive role of prostaglandin I2 generated by hyperosmotic saline in ethanol-induced gastric mucosal injury in rat.-The involvement of endogenous calcitonin gene-related peptide-"Gastroenterology. 116. A126 (1999)

K.Boku等人：“高渗盐水产生的前列腺素I2在乙醇诱导的大鼠胃粘膜损伤中的可能预防作用。-内源性降钙素基因相关肽的参与-”胃肠病学。

K. Boku, et al: "Possible preventive role of prostaglandin I2 generated by hyperosmotic saline in ethanol-induced gastric mucosal injury in rat."Gastroenterology. 116:. A126 (1999)

K. Boku 等人：“高渗盐水产生的前列腺素 I2 在乙醇诱导的大鼠胃粘膜损伤中的可能预防作用。”胃肠病学。

T.Saeki, et al: "Mechanism of prevention by capsaicin of ethanol-induced gastric mucosal injury-a study in the rat using intravital microscopy."Aliment Pharmacol Ther. 14(Suppl.1). 135-144 (2000)

T.Saeki 等人：“辣椒素预防乙醇引起的胃粘膜损伤的机制 - 使用活体显微镜对大鼠进行的研究。”Aliment Pharmacol Ther。

Takeo Saeki, et al: "Possible role of PGI2 in prevention ethanol-induced gastric mucosal injury by hyperosmotic saline. An intravital microscopic study."Jpn.J.Pharmacol.. 82(Suppl.I). 68P (2000)

Takeo Saeki 等人：“PGI2 在高渗盐水预防乙醇诱导的胃粘膜损伤中的可能作用。一项活体显微镜研究。”Jpn.J.Pharmacol.. 82（增刊 I）。

Takeo Saeki, et al: "The Preventive mechanism of hyperosmotic saline against the ethanol-induced gastric mucosal injyry."Jpn. J. Pharmacol.. 79(Suppl.I):. 53P (1999)

Takeo Saeki等人：“高渗盐水对乙醇引起的胃粘膜损伤的预防机制”。