ENTEROCHROMAFFIN-LIKE CELL CARCINOIDS IN THE RAT GASTRIC-MUCOSA FOLLOWING LONG-TERM ADMINISTRATION OF RANITIDINE
ENTEROCHROMAFFIN-LIKE CELL CARCINOIDS IN THE RAT GASTRIC-MUCOSA FOLLOWING LONG-TERM ADMINISTRATION OF RANITIDINE
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DOI：
10.1159/000200245
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发表时间：
1990-04-01
期刊：
影响因子：
3.2
通讯作者：
CARLSSON, E
中科院分区：
文献类型：
--
作者：
HAVU, N;MATTSSON, H;CARLSSON, E
长期服用一些长效胃酸分泌抑制剂与大鼠胃肠嗜铬样（ECL）细胞类癌的发生有关。有人认为，短效的，可克服的组胺H2受体阻滞剂，如雷尼替丁不会导致类癌。在本研究中，雌性大鼠（n = 100）接受组胺H2受体阻滞剂雷尼替丁（2 g/kg/天）给药2年。对所有大鼠（包括50只对照组）的胃标本进行嗜银细胞染色。在研究期间的不同时间，在单独的大鼠组中测量血浆胃泌素和雷尼替丁水平。雷尼替丁的平均血浆水平为37.5 μ mol/l，在午夜测量，此时预期食物摄入后的最大水平。产生的酸抑制与血浆胃泌素增加约3倍相关，并在整个研究期间持续存在。雷尼替丁处理导致胃ECL细胞明显增生。19只大鼠发现类癌，其中4只为微侵袭性类癌。在对照动物中未发现类癌。结果进一步支持了胃泌素机制，即大鼠胃粘膜中ECL细胞类癌的发展是长期高胃泌素血症的结果，而不是任何单个酸抑制药物的独特作用。
Long-term administration of some long-acting inhibitors of gastric acid secretion has been associated with the development of gastric enterochromaffin-like (ECL)-cell carcinoids in the rat. It has been argued that short-acting, surmountable histamine H2- receptor blockers such as ranitidine do not cause carcinoids. In this study, female rats (n = 100) were treated for 2 years with the histamine H2-receptor blocker ranitidine, 2 g/kg/day in the diet. Specimens from the stomachs of all rats, including 50 controls, were stained for argyrophil cells. Plasma gastrin and ranitidine levels were measured in separate groups of rats at different times during the study. The mean plasma level of ranitidine was 37.5 .mu.mol/l, measured at midnight when the maximal level after food intake was expected. The resulting acid inhibition was associated with an approximately 3-fold increase in plasma gastrin which persisted throughout the whole period of the study. The ranitidine treatment resulted in a pronounced hyperplasia of gastric ECL cells. In 19 rats carcinoids were found, 4 of which were micro-invasive. No carcinoids were found in the control animals. The results provide further support for the gastrin mechanism, i.e. that the development of ECL-cell carcinoids in the rat gastric mucosa is a consequence of prolonged hypergastrinaemia and is not a unique effect of any individual acid-inhibiting drug.