Long-term high-dose proton pump inhibitor administration to Helicobacter pylori-infected Mongolian gerbils enhances neuroendocrine tumor development in the glandular stomach.
Long-term high-dose proton pump inhibitor administration to Helicobacter pylori-infected Mongolian gerbils enhances neuroendocrine tumor development in the glandular stomach.
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发表时间：
2011
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通讯作者：
Hironobu Tsukamoto;T. Mizoshita;M. Sasaki;Takashi Mizushima;S. Tanida;K. Ozeki;Yoshikazu Hirata;T. Shimura;H. Kataoka;T. Kamiya;S. Nojiri;T. Tsukamoto;M. Tatematsu;T. Joh
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作者：
Hironobu Tsukamoto;T. Mizoshita;M. Sasaki;Takashi Mizushima;S. Tanida;K. Ozeki;Yoshikazu Hirata;T. Shimura;H. Kataoka;T. Kamiya;S. Nojiri;T. Tsukamoto;M. Tatematsu;T. Joh
质子泵抑制剂（PPI）通常用于控制上消化道疾病，通常长期应用。然而，人们对长期安全性以及胃神经内分泌肿瘤（NET）的癌症诱导和发展的可能性表示担忧。因此，我们在幽门螺杆菌（Hp）感染和未感染的蒙古沙鼠（MG）的腺胃中分析了PPI使用对肿瘤发展的组织学、免疫化学和血清学影响。将53只MG分为6组：Hp+25 PPI组、Hp+5 PPI组、Hp +25 PPI组、5 PPI组和对照组。高剂量Hp+25 PPI组和25 PPI组给予PPI（兰索拉唑）25 mg/kg/d，低剂量Hp+5 PPI组和5 PPI组给予5 mg/kg/d。在50或100周后，人道地处死动物，并使用针对嗜铬粒蛋白A（CgA）、胃泌素和胃抑制多肽（GIP）的抗体对腺胃样品进行组织学和表型评价。还检查了血清胃泌素水平。Hp+25 PPI、Hp+5 PPI、Hp和25 PPI组均出现NETs，但Hp感染与高剂量PPI给药之间无协同效应。Hp感染和高剂量PPI给药可显著升高血清胃泌素水平，但低剂量PPI对血清胃泌素水平无影响。NET的特征是表达CgA，但不表达胃泌素或GIP。总之，低剂量PPI对Hp感染和未感染的腺MG胃中癌和NETs的发展没有影响，表明临床安全性。然而，PPI在高剂量增加NET的发展和血清胃泌素在MG模型。
Proton pump inhibitors (PPIs) are routinely used for control of upper gastrointestinal disorders, often with long-term application. However, there has been some concern about the long-term safety and the possibility of cancer induction and development of neuroendocrine tumors (NET) in the stomach. We therefore analyzed the influence of PPI use on tumor development histologically, immunohistochemically, and serologically in the glandular stomachs of Helicobacter pylori (Hp)-infected and uninfected Mongolian gerbils (MGs). 53 MGs were divided into 6 groups: Hp+25PPI, Hp+5PPI, Hp, 25PPI, 5PPI, and controls. The high-dose Hp+25PPI and 25PPI groups received the PPI (lansoprazole) at 25mg/kg/day, and the low-dose Hp+5PPI and 5PPI groups were given 5mg/kg/day. After 50 or 100 weeks, animals were sacrificed humanely, and the glandular stomach samples were evaluated histologically and phenotypically, using antibodies against chromogranin A (CgA), gastrin and gastric inhibitory polypeptide (GIP). Serum gastrin levels were also examined. NETs occurred in the Hp+25PPI, Hp+5PPI, Hp, and 25PPI groups, but there was no synergistic effect between Hp-infection and high-dose PPI administration. Serum gastrin was increased statistically by Hp infection and high-dose PPI administration, but not influenced by the low-dose. The NETs featured expression of CgA, but not gastrin or GIP. In conclusions, PPI at low dose had no influence on development of carcinomas and NETs in the Hp-infected and uninfected glandular MG stomach, suggesting clinical safety. However, PPI at high dose increased NET development and serum gastrin in the MG model.