Helicobacter pylori alters gastric epithelial cell cycle events and gastrin secretion in mongolian gerbils
Helicobacter pylori alters gastric epithelial cell cycle events and gastrin secretion in mongolian gerbils
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DOI：
10.1016/s0016-5085(00)70413-6
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发表时间：
2000-01-01
期刊：
影响因子：
29.4
通讯作者：
Blaser, MJ
中科院分区：
文献类型：
--
作者：
Peek, RM;Wirth, HP;Blaser, MJ
背景与目的：幽门螺杆菌的人类定植可能通过改变胃上皮细胞周期事件和/或胃泌素分泌而增加远端胃腺癌的风险。本研究旨在确定幽门螺杆菌毒力相关特性是否影响胃腺癌啮齿动物模型中的细胞凋亡、增殖和胃泌素水平。方法：用H、Hp野生型或等基因cagA(-)、VacA(-)突变体攻击蒙古沙土鼠，分别用末端脱氧核苷酸转移酶介导的脱氧尿嘧啶核苷缺口末端标记法和增殖细胞核抗原免疫组织化学方法鉴定细胞的凋亡和增殖。用放射免疫法测定血清胃泌素水平。结果：野生型、cagA(-)、VacA(-)株感染后，胃上皮细胞转化率无明显差异。攻击后2~4周，幽门螺杆菌感染显著增加胃窦细胞凋亡率，之后细胞凋亡指数降至基线水平。相反，胃窦增殖率在接种后16~20周显著高于对照组，但在接种后40周下降，胃窦增殖与血清胃泌素水平显著相关，而胃窦细胞凋亡与急性炎症和淋巴滤泡呈负相关。结论：在Hp感染沙土鼠中，胃窦细胞凋亡增强是一种早期和短暂的细胞周期事件。上皮细胞增殖高峰较晚，且与胃泌素水平升高显著相关，提示幽门螺杆菌定植的粘膜上皮细胞的生长可能是由胃泌素依赖的机制介导的。
Background & Aims: Human colonization with Helicobacter pylori increases the risk for distal gastric adenocarcinoma, possibly by altering gastric epithelial cell cycle events and/or gastrin secretion. This study aimed to determine whether H, pylori virulence-related characteristics affect apoptosis, proliferation, and gastrin levels in a rodent model of gastric adenocarcinoma. Methods: Mongolian gerbils were challenged with H, pylori wild-type or isogenic cagA(-) and vacA(-) mutants, and apoptotic and proliferating cells were identified by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and proliferating cell nuclear antigen immunohistochemistry, respectively. Serum gastrin levels were determined by radioimmunoassay, Results: Gastric epithelial cell turnover was no different after infection with the wild-type, cagA(-), or vacA(-) strains. H, pylori infection significantly increased antral apoptosis 2-4 weeks after challenge, before apoptotic indices decreased to baseline. In contrast, antral proliferation rates were significantly higher 16-20 weeks after inoculation, but then decreased by 40 weeks, Antral proliferation was significantly related to serum gastrin levels, whereas antral apoptosis was inversely related to acute inflammation and lymphoid follicles, Conclusions: In H. pylori-infected gerbils, enhanced antral apoptosis is an early and transient cell cycle event. Epithelial cell proliferation peaks later and is significantly related to increased gastrin levels, suggesting that epithelial cell growth in H. pylori-colonized mucosa may be mediated by gastrin-dependent mechanisms.