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Ghrelin dynamics during the development of H.pylori-associated gastritis. - a novel possible non-invasive diagnostic marker for gastritis -

幽门螺杆菌相关性胃炎发展过程中的胃饥饿素动态。

基本信息

批准号：
15590686
负责人：
SUZUKI Hidekazu
金额：
$ 2.24万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590686/
关键词：
Helicobacter pylori Ghrelin Mongolian gerbil Chronic gastritis Gastric atrophy Pepsinogen myeloperoxidase body weight 摂食

项目摘要

Although ghrelin, a novel growth hormone-releasing peptide, localized mainly in the gastric fundus, is reported not only to accelerate food passage and gastrointestinal motility, but also to affect appetite and weight control, the regulation of gastric ghrelin secretion under the condition of gastric Helicobacter pylori(Hp) infection remains unknown.Study 1 : To investigate the plasma and gastric ghrelin levels in Mongolian gerbils with Hp colonization of the gastric mucosa.Methods. Gerbils orally inoculated with Hp were examined after the inoculation. To examine preproghrelin mRNA expression in the gastric mucosa, the cDNA encoding the gerbil preproghrelin and GAPDH homologue was isolated and a quantitative RT-PCR system was established. Results. In the gerbils showing Hp colonization (Hp group), the expression of preproghrelin mRNA and the total ghrelin levels were significantly decreased 17 and 23 weeks later (p<0.01). Although the number of ghrelin-immunoreactive cells decreased, a … More s the stomach weight increased, the gastric contents of total and active ghrelin in this group were the same as those in the controls. The gastric myeloperoxidase activity showed a positive correlation with the plasma ghrelin level. On the other hand, at 17 weeks, the plasma ghrelin level was significantly increased in the Hp group (p<0.05), suggesting a compensatory increase in the secretion of this peptide at this time-point. Conclusion. Gastric and plasma ghrelin dynamics was altered in response to Hp infection.Study 2 : To investigate the correlation between the plasma ghrelin levels and the extent of gastric mucosal atrophy in patients with chronic gastritis caused by H.pylori infection. Patients and Methods. Sixty-nine patients with dyspeptic symptoms were enrolled for the study. Of these, 41 patients were confirmed to become negative for H.pylori after therapy to eradicate the infection. The other 28 patients were diagnosed as positive for H.pylori infection. Blood samples were collected from all the patients after 12 hours' fasting, before upper GI endoscopy was performed. The plasma levels of total and active ghrelin, as well as the serum levels of pepsinogen I (PGI) and pepsinogen II (PGII) were measured by radioimmunoassay. Based on endoscopic assessment, the atrophic changes in the gastric mucosa were classified as open-type atrophy or closed-type atrophy.Results. There were no significant differences in the plasma total and active ghrelin levels between H.pylori-positive and H.pylori-eradicated (negative) patients. The serum levels of PGI were correlated well with the plasma levels of total ghrelin and active ghrelin. The ratio of serum PGI to PGII level(PG I/II ratio) was also correlated well with the plasma level of total ghrelin and active ghrelin. The plasma levels of total as well as active ghrelin were significantly decreased in patients with low PG levels as compared with those in patients with high PG levels(PG I>70ng/ml or PG I/II>3.0). The plasma levels of total as well as active ghrelin were also significantly decreased in patients with endoscopically diagnosed open-type atrophy as compared with those in patients with endoscopically diagnosed closed-type atrophy(p<0.01), especially in the H. pylori-eradicated cohorts.Conclusion. The plasma levels of ghrelin, which were correlated well with the serum levels of PG I as well as the PGI/II ratio, decreased with increasing extent of gastric mucosal atrophy, suggesting that it could be a potentially useful additional marker for chronic atrophic gastritis. Less

生长激素释放肽（ghrelin）是一种新的生长激素释放肽，主要定位于胃底，不仅能促进食物通过和胃肠运动，而且影响食欲和体重控制，但在胃幽门螺杆菌（Hp）感染条件下，胃ghrelin分泌的调节机制尚不清楚。目的探讨胃粘膜Hp定植蒙古沙土鼠血浆和胃Ghrelin水平的变化。接种后对经口接种Hp的沙土鼠进行检查。为了检测胃粘膜中preproghrelin mRNA的表达，分离了编码沙鼠preproghrelin和GAPDH同源物的cDNA，并建立了定量RT-PCR体系。结果Hp定植组17周和23周后前促生长素原mRNA表达和总促生长素水平均显著降低（p<0.01）。虽然生长激素释放肽免疫反应细胞的数量减少， ...更多信息胃重量增加时，胃内总Ghrelin和活性Ghrelin含量与对照组相同。胃髓过氧化物酶活性与血浆ghrelin水平呈正相关。另一方面，在17周时，Hp组的血浆ghrelin水平显著增加（p<0.05），表明在该时间点该肽分泌的补偿性增加。结论研究2：探讨幽门螺杆菌感染引起的慢性胃炎患者血浆ghrelin水平与胃粘膜萎缩程度的相关性。患者和方法。69例有消化不良症状的患者入组研究。其中，41名患者在根除感染的治疗后被证实为幽门螺杆菌阴性。其余28例患者被诊断为幽门螺杆菌感染阳性。所有患者空腹12小时后，在进行上消化道内镜检查前采集血样。用放射免疫法测定血浆中总Ghrelin和活性Ghrelin的水平，以及血清中胃蛋白酶原I（PGI）和胃蛋白酶原II（PGII）的水平。根据内镜检查结果，将胃粘膜萎缩分为开放型萎缩和闭合型萎缩。幽门螺杆菌阳性和幽门螺杆菌根除（阴性）患者的血浆总生长素和活性生长素水平无显著差异。血清PGI水平与血浆总Ghrelin和活性Ghrelin水平呈良好的相关性。血清PG Ⅰ/PG Ⅱ比值（PG Ⅰ/Ⅱ比值）与血浆总Ghrelin和活性Ghrelin水平也有良好的相关性。低水平PG患者血浆总Ghrelin和活性Ghrelin水平均显著低于高水平PG患者（PG I> 70 ng/ml或PG I/II>3.0）。开放型萎缩患者血浆总ghrelin和活性ghrelin水平也明显低于闭合型萎缩患者（p<0.01），尤其是H.幽门根除队列。血浆ghrelin水平与血清PG I水平和PGI/II比值具有良好的相关性，随着胃粘膜萎缩程度的增加而降低，表明其可能是慢性萎缩性胃炎的潜在有用的额外标记物。少