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

虽然Ghrelin是一种新的生长激素释放肽，主要定位于胃底，不仅可以促进食物通过和胃肠运动，还可以影响食欲和体重控制，但在胃幽门螺杆菌(Hp)感染条件下Ghrelin的分泌调节尚不清楚。研究1：了解Hp定植于胃粘膜的蒙古沙土鼠血浆和胃Ghrelin水平。口服接种幽门螺杆菌的沙土鼠在接种后进行检查。为了检测胃粘膜中前促生长素基因的表达，分离了编码沙土鼠前促红细胞生成素和谷氨酸脱氢酶同源物的基因，建立了定量RT-PCR体系。结果。在Hp定植沙土鼠(Hp组)中，Hp感染后17周和23周，前Proghrelin mRNA表达和总Ghrelin水平均显著降低(p&lt；0.01)。虽然Ghrelin免疫反应细胞的数量减少了，但…随着S剂量的增加，胃重量增加，胃液中Ghrelin总量和活性与对照组无明显差异。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水平显著升高(p&lt；0.05)，提示在该时间点该肽的分泌出现代偿性增加。结论。研究2：探讨幽门螺杆菌感染所致慢性胃炎患者血浆胃促生长素水平与胃粘膜萎缩程度的相关性。病人和方法。69名有消化不良症状的患者参加了这项研究。在这些患者中，有41名患者在根除感染的治疗后被确认为幽门螺杆菌阴性。其余28例患者均为幽门螺杆菌阳性。所有患者禁食12小时后，于上消化道内窥镜检查前采集血样。用放射免疫法测定血浆总Ghrelin和活性Ghrelin水平，以及血清胃蛋白酶原I(PGI)和胃蛋白酶原II(PGII)水平。根据胃镜检查结果，将胃粘膜萎缩性改变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)患者的血浆总生长激素水平和活性生长激素水平无显著差异。血清PGI水平与血浆总Ghrelin和活性Ghrelin水平呈正相关。血清PGI/PGII比值(PG I/II比值)与血浆总Ghrelin和活性Ghrelin水平呈正相关。低PG组血浆总Ghrelin和活性Ghrelin水平显著低于高PG组(PG I和GT；70 ng/ml或PG I/II和GT；3.0)。胃镜诊断为开放型萎缩的患者血浆总Ghrelin和活性Ghrelin水平也显著低于胃镜诊断为闭合型萎缩的患者(p&lt；0.01)，尤其是在Hp根除的队列中。血浆Ghrelin水平与血清PG I水平及PGI/II比值呈正相关，随着胃粘膜萎缩程度的加重而降低，提示Ghrelin可作为慢性萎缩性胃炎的辅助标志物。较少

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