Gastrin enhances gastric mucosal integrity through cyclooxygenase-2 upregulation in rats
Gastrin enhances gastric mucosal integrity through cyclooxygenase-2 upregulation in rats
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DOI：
10.1152/ajpgi.00006.2002
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发表时间：
2002-12-01
影响因子：
4.5
通讯作者：
Hori, M
中科院分区：
文献类型：
--
作者：
Komori, M;Tsuji, S;Hori, M
胃泌素、pg和生长因子在维持胃肠道粘膜完整性中起重要作用。环加氧酶（COX-1和COX-2）是PG合成的关键酶。本研究旨在阐明胃泌素对胃粘膜的保护作用机制。空腹大鼠皮下给予胃泌素17加或不加胃泌素受体拮抗剂YM022预处理。Western blot检测肝素结合表皮生长因子样生长因子（HB-EGF）和COX-2的表达。另一系列实验研究了1)胃粘膜中PGE(2)的水平，2)胃泌素对酸化乙醇对胃损伤的保护作用，3)特异性hb - egf中和抗体对胃泌素诱导的COX-2表达的影响，以及4)特异性COX-2抑制剂NS-398对PGE(2)合成和胃泌素对粘膜的保护作用。胃泌素剂量依赖性地增加HB-EGF、COX-2表达和PGE(2)水平，减轻胃损伤。然而，用YM022剂量依赖性预处理可消除胃泌素的这种作用。一种特异性hb -EGF中和抗体和一种EGF受体抑制剂可降低胃泌素诱导的COX-2表达。NS-398阻断胃泌素诱导的PGE(2)合成和粘膜保护。综上所述，本研究表明胃泌素通过部分由HB-EGF介导的COX-2和PGE(2)上调大鼠胃粘膜完整性。
Gastrin, PGs, and growth factors have important roles in maintaining gastrointestinal mucosal integrity. Cyclooxygenases (COX-1 and COX-2) are the key enzymes involved in PG synthesis. This study aimed to clarify the mechanisms of gastric mucosal protection by gastrin. Fasted rats were administered subcutaneous gastrin 17 with or without gastrin receptor antagonist YM022 pretreatment. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) and COX-2 expression were examined using Western blot analysis. Another series of experiments investigated 1) PGE(2) levels in gastric mucosa, 2) the protective action of gastrin against gastric damage by acidified ethanol, 3) the effects of a specific HB-EGF-neutralizing antibody on gastrin-induced COX-2 expression, and 4) the effects of a specific COX-2 inhibitor NS-398 on PGE(2) synthesis and the mucosal protection afforded by gastrin. Gastrin dose-dependently increased HB-EGF, COX-2 expression, and PGE(2) levels and reduced gastric damage. However, pretreatment with YM022 dose-dependently abolished such effects of gastrin. A specific HB-EGF-neutralizing antibody and an EGF receptor inhibitor decreased gastrin-induced COX-2 expression. NS-398 blocked gastrin-induced PGE(2) synthesis and mucosal protection. In conclusion, this study demonstrates that gastrin enhances gastric mucosal integrity through COX-2, which is partially mediated by HB-EGF, and PGE(2) upregulation in rats.