Low-dose aspirin reduces the gene expression of gastrokine-1 in the antral mucosa of healthy subjects
Low-dose aspirin reduces the gene expression of gastrokine-1 in the antral mucosa of healthy subjects
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DOI：
10.1111/j.1365-2036.2008.03793.x
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发表时间：
2008-09-15
影响因子：
7.6
通讯作者：
Nardone, G.
中科院分区：
文献类型：
--
作者：
Martin, G.;Wex, T.;Nardone, G.
背景胃动素1（GKN 1）是正常胃组织中含量最丰富的转录因子之一，幽门螺杆菌感染后GKN 1表达下调。阿司匹林（Aspirin，阿萨）是心血管事件的二级预防药物，但在摄入ASA后1 ~ 2 h内可引起胃十二指肠粘膜损伤。幽门阴性的志愿者每天服用100 mg阿萨，持续1周，并接受多次上消化道内窥镜检查。GKN 1的表达进行了分析，在胃窦和胃体粘膜定量逆转录聚合酶链反应，免疫印迹和免疫组化（IHC）。结果Gastrokine 1在胃窦粘膜和胃体粘膜中的表达相似。使用低剂量阿萨导致显著降低（3.07 a.u.相对于0.23 a. u.，胃窦部GKN 1转录水平在第7天增加2倍（P < 0.001），胃体部GKN 1转录水平增加2倍（P < 0.005）。Western blot和IHC证实了这些蛋白水平的变化。GKN 1在胃窦黏膜中表达呈囊泡状，转染GKN 1的人胃腺癌细胞系证实了这一点。结论低剂量阿萨特异性下调胃窦黏膜中GKN 1的表达。
Background Gastrokine 1 (GKN1), one of the most abundant transcripts in normal stomach, is down-regulated by Helicobacter pylori infection. Aspirin (ASA), which is often used for secondary prevention of cardiovascular events, can damage gastric-duodenal mucosa within 1 or 2 h of ingestion.Aim To study the gastric mucosal expression of GKN1 during acute low-dose ASA consumption.Methods Ten H. pylori-negative human volunteers took 100 mg ASA per day for 1 week, and underwent multiple upper GI endoscopies. GKN1 expression was analysed in antral and corpus mucosa by quantitative reverse-transcriptase polymerase chain reaction, western blot and immunohistochemistry (IHC). Gastric mucosal damage was detected endoscopically and histologically.Results Gastrokine 1 was similarly expressed in both antral and corpus mucosa. The use of low-dose ASA led to a significant decrease (3.07 a.u. vs. 0.23 a.u., P < 0.001) in antrum at day 7, while GKN1 transcript levels in corpus mucosa were slightly elevated (twofold, P < 0.005). Western blot and IHC confirmed these changes at the protein level. Furthermore, IHC revealed a vesicular staining pattern in the cytoplasm for GKN1 that was confirmed by transfected human gastric adenocarcinoma cell line expressing GKN1.Conclusion Our data demonstrated that low-dose ASA downregulates GKN1 expression specifically in antral mucosa.