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

胃饥饿素（ghrelin）是一种主要存在于胃底的新型生长激素释放肽，据报道不仅能加速食物通过和胃肠蠕动，还能影响食欲和体重控制，但胃幽门螺杆菌（Hp）感染情况下胃饥饿素分泌的调控机制尚不清楚。研究1：探讨Hp在蒙古沙鼠胃粘膜定植后血浆和胃饥饿素水平的变化。经口腔接种Hp的沙鼠接种后进行检查。为了检测胃粘膜中preproghrelin mRNA的表达，分离沙鼠preproghrelin和GAPDH同源基因的cDNA，建立定量RT-PCR体系。结果。Hp定殖的沙鼠（Hp组）在17周和23周后，胃饥饿素前蛋白mRNA的表达和总胃饥饿素水平显著降低（p<0.01）。随着胃重的增加，胃促生长素免疫反应细胞数量减少，胃促生长素总含量和胃促生长素活性含量与对照组基本一致。胃髓过氧化物酶活性与血浆胃饥饿素水平呈正相关。另一方面，在17周时，Hp组血浆ghrelin水平显著升高（p<0.05），提示该肽在该时间点的代偿性分泌增加。结论。Hp感染后，胃和血浆胃饥饿素动力学发生改变。研究2：探讨幽门螺杆菌感染所致慢性胃炎患者血浆ghrelin水平与胃黏膜萎缩程度的相关性。患者和方法。69名有消化不良症状的患者参加了这项研究。其中，41名患者在接受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。所有患者在禁食12小时后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总胃饥饿素和活性胃饥饿素水平以及血清胃蛋白酶原I （PGI）和胃蛋白酶原II （PGII）水平。经内镜检查，胃粘膜萎缩变化分为开放式萎缩和闭合型萎缩。幽门螺杆菌阳性和根除幽门螺杆菌（阴性）患者血浆总胃饥饿素和活性胃饥饿素水平无显著差异。血清PGI水平与血浆总胃饥饿素和活性胃饥饿素水平有良好的相关性。血清PGI / PGII水平比值（PG I/II比值）与血浆总胃饥饿素和活性胃饥饿素水平也有良好的相关性。与PG水平高的患者（PG I>70ng/ml或PG I/II>3.0）相比，PG水平低的患者血浆总胃饥饿素和活性胃饥饿素水平显著降低。内镜下诊断为开放式萎缩的患者血浆总胃饥饿素和活性胃饥饿素水平也明显低于内镜下诊断为封闭式萎缩的患者（p<0.01），尤其是幽门螺杆菌根除组。血浆ghrelin水平与血清PGI水平及PGI/II比值密切相关，随着胃粘膜萎缩程度的增加而下降，提示它可能是慢性萎缩性胃炎的潜在有用的附加标志物。少

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