白细胞介素-1β介导幽门螺杆菌相关胃癌发生的实验研究  

Experimental study on Helicobacter pylori-related gastric carcinogenesis mediated by interleukin-lβ

作　　者：郭涛[1] 钱家鸣[1] 赵雩卿[1] 李晓波[2] 张建中[3] 

机构地区：[1]中国医学科学院中国协和医科大学附属北京协和医院消化科,北京100730 [2]北京大学肝病研究所 [3]中国疾病预防控制中心传染病预防控制所传染病诊断室

出　　处：《中华消化杂志》2008年第4期217-220,共4页Chinese Journal of Digestion

基　　金：国家自然科学基金资助项目（30270600）

摘　　要：目的探讨白细胞介素（IL）-1β在幽门螺杆菌（Hp）相关胃癌发生中可能的作用机制。方法以人胃永生化上皮细胞株（GES-1）和胃癌细胞株（AGS）为研究对象，采用四甲基偶氮唑盐比色法测定IL-1β对细胞增殖的影响，流式细胞术碘化丙啶单染法测定IL-1β对Hp（NCTC11637）诱导细胞凋亡的影响。分别应用RT-PCR法和流式细胞术（荧光定量法）检测IL-1β对细胞环氧合酶-2（COX-2）mRNA和蛋白表达的影响。以兔离体壁细胞为研究对象，应用14C-氨基比林（14C-AP）摄取法检测IL-1β对组胺刺激壁细胞酸分泌的影响，应用RT-PCR法分析IL-1β对壁细胞H^＋-K^＋-ATP酶a亚基mRNA表达的影响。结果IL-1β能刺激GES-1和AGS细胞增殖，抑制Hp诱导的GES-1和AGS细胞凋亡。IL-1p能诱导GES-1COX-2表达，上调AGS细胞COX-2表达；诱导GES-1和AGS细胞COX-2蛋白表达上调（分别由1．016±0．020和1．070±0．034上调至1．485±0．220和1．501±0．182）。IL-1β能抑制组胺刺激的离体壁细胞酸分泌，同时伴H^＋-K^＋-ATP酶a亚基mRNA表达下调。结论IL-1β可能通过两条途径在Hp相关胃癌发生中起作用：上调COX-2表达，破坏胃上皮细胞增殖、凋亡平衡和下调H^＋-K^＋-ATP酶表达以抑制壁细胞分泌。Objective To investigate the potential mechanism of interleukin-lβ （IL-1β） in H. pylori-related gastric carcinogenesis. Methods Human gastric cancer cell line （AGS）, human gastric epithelial cell line （GES-1） and isolated parietal cells were treated with exogenous IL-1β （10 ng/ml） in the presence or absence of H. pylori （NCTC 11637）. Cell proliferation and apoptosis were determined by MTT assay and flow cytometry, respectively. Expressions of cyclooxygenase-2 （COX-2） mRNA and protein were examined using RT-PCR and flow cytometry, respectively. Acid secretion by parietal cells was tested using 14C-aminopyrine （14 C-AP） accumulation indirectly. H^＋/K^＋ ATPase a subunit mRNA expression was assessed using RT-PCR. Results The cell proliferation and H. pylori-related apoptosis in both GES-1 and AGS cell lines were stimulated and inhibited by IL-1β. IL-1β induced expression and upregulation of COX-2 mRNA in GES-1 and AGS cell lines, respectively. In addition, IL-1β continuously inhibited the ability of histamine-stimulated 14 C-AP accumulation of isolated parietal cells accompanied by down-regulation of H^＋/K4- ATPase mRNA expression. Conclusions It suggests that IL-1β play an important role in H. pylori-related gastric carcinogenesis through two pathways： ①to interfere gastric epithelial cell growth by up-regulating COX-2 expression, ②to inhibit acid secretion from parietal cell by down-regulating H＋/K＋ ATPase expression.

关 键 词：胃肿瘤 白细胞介素-1 幽门螺杆菌 

分 类 号：R686[医药卫生—骨科学]