胃十二指肠疾病与血浆激素关系的初步研究

对64例胃十二指肠疾病患者(包括慢性残表性胃炎23例,萎缩性胃炎5例,胃溃疡10例,十二指肠溃疡14例及胃癌12例)的血浆生长抑索(SS)、血管活性肠肽(VIP)、胃动素(MTL)及血清胃泌素(Gas)的研究表明,血浆SS水平在胃十二指肠溃疡组及胃癌组均低于正常对照组(P<0.001);血浆VIP浓度在胃溃疡时升高最明显,与正常组及各疾病组比较均有显著性差异(P<0.01);十二指肠溃疡及胃癌组的血浆MTL含量均高于正常对照组(P<0.05);血清Gas水平在浅表性胃炎和萎缩性胃炎时均高于正常对照组(P<0.01).     

胃泌素及其受体与胃癌关系的研究进展

胃泌素主要由胃窦及小肠上段黏膜的G细胞分泌,其受体分布在多种器官组织中.胃泌素及其受体具有调节细胞生长、分化,抑制细胞凋亡,促进细胞增生、侵袭、转移的功能.研究表明,胃泌素及其受体参与包括胃癌在内的多种肿瘤的发生、发展.胃泌素及其受体还可作为胃癌早期诊断的一个重要指标,同时也可能是胃癌治疗的潜在靶点.本文就胃泌素及其受体与胃癌的发生、发展关系作一综述.     

Influence of hypergastrinemia secondary to long-term proton pump inhibitor treatment on ECL cell tumorigenesis in human gastric mucosa

Proton pump inhibitor (PPI) therapy causes hypergastrinemia, which could promote the development and progression of neuroendocrine tumors (NETs). Concerns have been raised about the safety of long-term PPI use due to a possible increased risk of NETs. This study aimed to investigate the association between hypergastrinemia and the risk of NETs. Twenty outpatients presenting with serum gastrin levels greater than 400 pg/mL after long-term PPI treatment were registered in this study. Immunohistochemical analyses for chromogranin A (CgA), Ki67, gastrin and CCK/B gastrin receptor (CCKBR) were performed, and positive cell numbers were counted. There were no NET or gastric epithelial neoplasia cases observed among any of the 20 patients examined throughout the PPI treatment period. Histologically, ECL cell hyperplasia were shown in all patients. However, no relationship was found between serum gastrin levels and the number of CgA positive ECL cells. There was also no relationship between serum gastrin levels and the proportion of Ki67 positive cells or the density of CCKBR positive cells. The data indicate no relationship may exist between NETs and hypergastrinemia secondary to PPI treatment in patients having no, or mild, atrophic gastritis.     

Influence of Exposure to Extremely Low Frequency Magnetic Field on Neuroendocrine Cells and Hormones in Stomach of Rats

Extremely low frequency magnetic fields (ELF-MF) have the ability to produce a variety of behavioral and physiological changes in animals. The stomach, as the most sensitive part of the neuroendocrine organ of the gastrointestinal tract, is crucial for the initiation of a full stress response against all harmful stress. Thus, the purpose of this study was to examine whether ELF-MF stimuli induce changes in the activity of neuroendocrine cells, considering their involvement in endocrine or paracrine effect on surrounding cells. The exposure to ELF-MF (durations of 24 h and 1 or 2 weeks, 60 Hz frequency, 0.1 mT intensity) altered the distribution and occurrence of gastrin, ghrelin and somatostatin-positive endocrine cells in the stomach of rats. The change, however, in the secretion of those hormones into blood from endocrine cells did not appear significantly with ELF-MF exposure. Comparing with sham control, ELF-MF exposure for 1 and 2 week induced an increase in BaSO₄ suspension propelling ratio of gastrointestinal tract, indicating that ELF-MF affects gastrointestinal motility. Our study revealed that ELF-MF exposure might influence the activity of endocrine cells, an important element of the intrinsic regulatory system in the digestive tract. The pathophysiological character of these changes and the mechanism responsible for neuroendocrine cell are still unclear and require further studies.     

Presence of Gastric Autoantibodies Impairs Gastric Secretory Function in Patients with Helicobacter pylori-positive Duodenal Ulcer

Background: Although the association between Helicobacter pylori infection and gastric autoimmunity is now well established, to date little is known about the significance of anticanalicular autoantibodies in patients with duodenal ulcer (DU). We therefore investigated the prevalence of serum antiparietal cell autoreactivity in DU patients as well as the relationship between these autoantibodies, gastric histopathology and gastric secretory function in this setting. Methods: Forty-one consecutive patients with H. pylori-positive DU were initially recruited. In all patients, basal (BAO) and pentagastrin stimulated acid output (PAO), fasting and meal-induced serum gastrin levels, as well as serum pepsinogen I concentrations, were measured. Antral and body gastritis was evaluated according to the Sydney system. Serum anticanalicular autoreactivity was determined by the indirect immunoperoxidase technique. Results: Serum anticanalicular autoantibodies were found in 7 out of 34 patients (20%). The presence of these antibodies was associated with a significantly higher grade of body gastritis (activity: 1.9 versus 0.9) as well as with significantly higher fasting and meal stimulated gastrin levels (mean fasting gastrin, 76.4 (15.2) pg/ml versus 59.3 (20.5) pg/ml). In addition, PAO values were significantly lower in patients with gastric autoantibodies than in those without this autoreactivity (mean 0.35 (0.16) mmol kg^-1 h^-1 versus 0.49 (0.16) mmol kg^-1 h^-1). In contrast, no significant differences were found between patients with and without anticanalicular autoantibodies as regards fasting serum pepsinogen I concentrations. Conclusions: Serum anticanalicular autoantibodies can be detected in 20% of patients with DU and are associated with a more severe pattern of body gastritis, higher gastrin levels and decreased peak acid secretion values. Their presence could account for the normal or reduced acid output which can be seen in a subset of DU patients.     

胃泌素释放肽前体融合蛋白的制备及其在肿瘤研究中的应用

目的克隆胃泌素释放肽前体(pro-GRP)基因、构建重组质粒pGEM-T-pro-GRP和表达载体PMS-31b-pro-GRP、在大肠杆菌中热诱导表达并制备融合蛋白。方法从BGC823胃癌细胞中提取总RNA,利用pro-GRP特异引物,扩增人pro-GRP分子的cDNA全长。将pro-GRP基因定向克隆于pGEM-T载体转化JM109,DNA测序鉴定基因序列。将pro-GRP基因定向克隆于原核高效表达载体PMS-31b,转化大肠杆菌POP2136经42℃热诱导表达MS2-pro-GRP融合蛋白。将融合蛋白分离纯化后,十二烷基硫酸钠聚丙烯酰胺凝胶电泳(SDS-PAGE)凝胶鉴定。结果经聚合酶链反应(PCR)扩增成功获得210bp的pro-GRP基因,目的基因序列正确。SDS-PAGE显示热诱导后表达的融合蛋白分子量约为18000。结论成功克隆pro-GRP基因,并表达和纯化了PMS-31b-pro-GRP融合蛋白,为建立pro-GRP检测方法奠定了基础。     

大肠癌细胞胃泌素的表达与Fas、FasL的关系

目的研究大肠癌细胞胃泌素（GAS）的表达与Fas、FasL的关系。方法采用免疫组化方法检测60例大肠癌细胞的GAS、Fas、FasL的表达情况，并分析他们之间的关系。结果在60例大肠癌细胞中，FasL在DukesC、D期的阳性表达率明显高于DukesA、B期的阳性表达率，差异有统计学意义（P〈0.05）。并且FasL的表达随着GAS表达增强而增强，呈明显的正相关（P〈0.05）。而Fas的表达在各临床病理特征之间无明显区别，与GAS的表达也无相关性。结论GAS在大肠癌细胞中可能是通过提高FasL的表达来杀伤淋巴细胞，从而逃避免疫监视，促进增殖和转移。     

Gastrin Receptor Gene Expression in Several Human Carcinomas

Gastrin has been shown to enhance the growth of various human tumors. The present study was designed to examine the gastrin receptor gene expression in various human carcinoma cell lines and in surgically resected carcinoma tissues. By Northern blot analysis, gastrin receptor mRNA was detected in 3 out of 7 small cell lung carcinoma cell lines. Gastrin receptor mRNA was also expressed in one out of 8 colon carcinoma cell lines and 2 out of 10 colon carcinoma tissues. Moreover, one of two small cell carcinoma cell lines of the stomach clearly expressed gastrin receptor mRNA. However, none of the gastric adenocarcinoma cell lines or surgically resected gastric adenocarcinomas tested had any detectable expression of gastrin receptor gene. These findings may suggest a role of gastrin receptor in the growth and differentiation of certain human carcinomas.     

Non-nutritive sucking does not increase blood levels of gastrin, motilin, insulin and insulin-like growth factor 1 in premature infants receiving enteral feedings

Non-nutritive sucking in premature infants accelerates weight gain for unclear reasons. The effects of non-nutritive sucking on enteral hormone secretion may augment digestion and/or absorption of nutrients. Blood concentrations of gastrin, motilin, insulin and insulin-like growth factor-1 were measured before and 72 h after the initiation of nasogastric feedings in 21 premature infants randomly assigned to either a non-nutritive suckling or control group. Gastrin and motilin concentrations increased significantly after feedings in all infants (mean +/- SEM) (gastrin, 41 +/- 4 to 73 +/- 9 pg/ml, p < 0.01; motilin, 141 +/- 5 to 181 +/- 3 pg/ml, p < 0.01) Pre- and post-feed insulin concentrations were greater in the non-nutritive sucking group receiving bolus feeds than in control infants who were bolus-fed (P < 0.01). Non-nutritive sucking in premature infants does not appear to alter blood concentrations of motilin, gastrin, insulin or insulin-like growth factor-1 three days after initiation of feedings. If changes in the secretion of these hormones are induced by non-nutritive sucking, they may be at a local paracrine level.     

不同组别肝癌动脉内插管化疗栓塞后血清胃泌素变化的意义

本文通过对不同肝癌组别不同治疗组别的对照研究，分析了２９例共３７次肝癌患者接受动脉内插管化疗栓塞术前术后血清胃泌素测定值的结果，男性２８例，女性１例，平均年龄４７．７岁。肝癌组１３例，接受１８次治疗；肝癌合并肝硬化腹水组１６例，接受１９次治疗，在治疗方式上分成肝固有动脉内治疗组和肝动脉加其它动脉内治疗组；以未梢血管栓塞组和未梢血管加主干栓塞组，每组内均数比较采用ｔ检验，每组之间采用近似Ｆ检验，结果