胃壁细胞胃泌素受体及受体后信号传递的研究

胃泌素 ( gastrin)是一类能引起酸分泌的胃肠道多肽激素 ,其按所含氨基酸数可分为 G- 34、G- 1 7、G-1 4,分别称为大胃泌素、胃泌素和小胃泌素 ,它由 G细胞分泌。胃泌素的主要生理作用为促进胃酸分泌 ,并与组胺及乙酰胆碱有协同作用 ,它可直接通过与壁细胞上胃泌素受体结合而促进泌酸 ,或可通过激活 ECL细胞释放组胺而介导 [1]。胃泌素刺激壁细胞酸分泌以及 ECL细胞释放组胺都是通过相同的胃泌素受体 ,而胃泌素对 ECL细胞又表现出营养作用 ,Kinoshita等 [2 ]比较了壁细胞与 ECL细胞内胃泌素受体信号传导通路 ,认为壁细胞与 ECL细胞…     

大黄脾虚模型大鼠胃壁细胞的超微结构观察

[目的]探讨大黄脾虚模型大鼠即时分离的胃壁细胞超微结构的变化.[方法]脾虚模型采用大黄泻下方法,酶法(Pronase-EDTA)消化分离及离心纯化大鼠胃壁细胞,透射电镜观察模型组与正常组壁细胞的超微结构变化.[结果]正常组大鼠即时分离的胃壁细胞胞质内可见大量的线粒体和散在的囊泡结构;脾虚组大鼠胃壁细胞电镜下可见明显扩张的分泌小管,小管内可见增长密集的微绒毛,囊泡状结构少见,未见线粒体结构异常.[结论]大黄脾虚模型大鼠胃壁细胞超微结构呈应激状态,可能致其自身对攻击因子敏感性增高,进而导致胃黏膜的易损性增强.     

大鼠胃壁细胞的分离方法

胃粘膜的壁细胞属于高度特异的终末分化细胞［１］,主要功能是分泌胃酸,以便为壁细胞研究提供理想的实验工具,为临床治疗胃肠道疾病提供新的途径和方法［２－５］．大鼠比兔、狗等动物价廉易得,而且用整体大鼠做胃溃疡模型、进行泌酸实验与其他动物相比也是最多的．直到目前大鼠胃壁细胞的分离方法国内尚未见报道．不同种属动物胃壁细胞分离的总的原则虽然一致,但是具体操作方法可因动物种属不同而不同．比如所用消化酶的种类、消化方式、消化时间等可有较大差异．对此我们进行了实践,现报道如下．１　材料和方法１．１　材料　ＨＺＳ…     

胃泌素及其受体与胃癌关系研究进展

多数研究认为 ,某些胃癌组织或细胞株有胃泌素及其受体基因表达 ,胃泌素通过受体介导的细胞内信号传导途径促进胃癌的发生与生长 ;胃癌患者血浆、胃液中胃泌素水平升高对预后判断可能有一定临床参考价值 ,胃泌素及其受体拮抗剂将为胃癌内分泌治疗开辟新的途径。     

慢性胃病脾虚患者胃窦粘膜胃泌素细胞和分泌生长抑素细胞的变化及其意义

目的：观察以慢性胃病为主的脾虚患者胃窦粘膜分泌胃泌家(Gas)细胞(G细胞)、生长抑素(SS)细胞(D细胞)与脾虚证发生的关系。方法：将84例脾虚患者分为脾胃虚寒组、脾虚夹热组、胃阴不足组、脾胃湿热组、肝胃不和组，应用免疫组化技术标记胃窦粘膜G、D细胞，并定量分析。结果：以慢性胃病为主的脾虚证患者G、D细胞数均减少，D细胞面积缩小，G/D细胞数和细胞面积比值均增高(P＜0．05)。结论：G、D细胞的变化可能是慢性胃病脾虚证胃肠功能障碍的一个重要病理机制。     

胃泌素受体作为分子靶向在肿瘤中的表达及应用

胃泌素(Gas)广泛存在于胃肠道和胰腺组织内,在调控生理功能及某些疾病的发病机制中都有重要作用.近来研究表明,Gas能够促进肿瘤尤其是胃癌、大肠癌等消化系肿瘤的发生、发展.Gas的生物作用主要通过CCK受体介导,Gas mRNA在一些CCK受体阳性的小细胞肺癌,乳腺癌,卵巢癌,不同来源的癌干细胞,已经发现有表达,可能作为这些肿瘤自分泌生长调节的指示指标.对于过表达胃泌素受体的肿瘤,可以给予胃泌素多肽及类似物作放射性标记或连接细胞毒药物,体内用闪烁成像法跟踪显像,从而用于肿瘤的诊断和治疗.     

胃壁细胞的研究进展

胃窦黏膜由单层柱状上皮、固有膜和黏膜肌构成。单层柱状上皮在胃小凹处凹入，小凹底与位于固有膜内的幽门腺细胞相连，其中有产生盐酸的壁细胞、产生胃蛋白酶的主细胞、产生含丰富黏多糖类黏液的黏液细胞等多种细胞。壁细胞与泌酸功能相关。随着细胞生物学、分子生物学和各种显微研究技术的不断完善，对壁细胞的认识也有了长足的提高。现就有关壁细胞的一些研究进展综述如下。     

益气增液颗粒对脾虚泄泻大鼠血清胃泌素及血浆胃动素影响的研究

目的：探讨益气增液颗粒对脾虚泄泻SD大鼠血清胃泌素（GAS）、血浆胃动素（MOT）的影响；方法：用放射免疫法测定200％大黄煎液造成的脾虚泄泻SD大鼠血清GAS，血浆MOT的含量。结果：脾虚模型组大鼠血清GAS含量低于正常对照组（P＜0．01），阳性对照组和益气增液颗粒中，高剂量组与脾虚模型组相比均P＜0．05；益气增液颗粒3个剂量组与阳性对照组相比均P＞0．05；脾虚模型组大鼠血浆MOT含量明显低于正常对照组（P＜0．01），阳性对照组和益气增液颗粒3个剂量组与脾虚模型组相比P＜0．05及P＜0．01；益气增液颗粒高剂量组与阳性对照组相比有统计学意义（P＜0．01）。结论：GAS、MOT含量变化很可能是脾虚泄泻的一项重要的病理生理学改变，而益气增液颗粒对脾虚泄泻SD大鼠GAS、MOT含量变化明显的调节作用。     

大肠癌胃泌素表达、受体状况及血清水平的临床意义

我们采用放射免疫、免疫组化及放射性配体结合试验对７０例大肠癌进行了血清胃泌素（ＳＧ）,肿瘤组织胃素（ＧＡＳ）表达及胃泌素受体（ＧＲ）的检测,并对其临床意义进行了分析。材料及方法一、对象大肠癌７０例,男４５例,女２５例,年龄１７～７５岁,平均４８±２３．６岁,其中结肠癌２６例,直肠癌４４例。病理类型：乳头状腺癌１６例,管状腺癌２７例,粘液腺癌１３例,印戒细胞癌８例,未分化腺癌６例。Ｄｕｋｅ分期,Ａ期１２例、Ｂ期１７例、Ｃ期２６例、Ｄ期１５例。行根治性切除５６例,姑息性切除１４例。全组均无消化性溃疡…     

Comparison of cAMP System in Parietal Cells from Rat and Guinea Pig

Adenylyl cyclase activity, cAMP content, and activation of cAMP-dependent protein kinase were measured in rat and guinea pig parietal cells isolated by the same procedure. Incubation of parietal cells with histamine resulted in aminopyrine uptake, stimulation of adenylyl cyclase activity, accumulation of intracellular cAMP, and activation of cAMP-dependent protein kinase. In addition, aminopyrine uptake and the cAMP system were stimulated in rat cells by epinephrine, whereas guinea pig cells were unresponsive to epinephrine. It is suggested that there may be differences between the two species with regard to receptors on the parietal cells.     

Morphometric Studies of Human Parietal Cells before and 7 Days after Proximal Gastric Vagotomy

In nine patients, acid titration tests and gastric biopsy specimens were studied before proximal gastric vagotomy (PGV) and 1 week after the operation. When postoperative biopsy specimens were compared with the preoperative ones, no change was found in the thickness of the mucosa. The volume fraction of the mucosa made up of parietal cells was significantly reduced (p < 0.01) from 13.8% before PGV to 11.2% after PGV (median values). Both before and after the operation, stimulation with pentagastrin was followed by a significant increase in the relative volume of microvilli in parietal cells and a significant reduction of the relative volume of tubulovesicular structures. The magnitude of this ultrastructural response to pentagastrin was similar before and after PGV. The relative volume of lysosome-like structures was significantly increased in parietal cells postoperatively. With this exception, no significant alteration was found when comparing the ultrastructure before and 7 days after PGV.     

Famotidine Prevents Deep Histologic Lesions Induced by 0.6N HCl in Rat Gastric Mucosa: Role of Parietal Cells

The assessment of the protective actions of H₂-receptor antagonists against gastric mucosal lesions by necrotizing agents relies on the gross observation of the gastric mucosa only. We examined the activity of famotidine against 0.6 N HCl-induced damage and the role of parietal cells by light and transmission electron microscopy. Rats received famotidine 0.3–10 mg/kg intragastrically. Sixty minutes later 0.6 N HCl (1 ml/rat) was given and after an additional 30 min the stomachs were removed. Macroscopically visible lesions were measured. Histologic lesions were scored on the basis of the depth. The ultrastructure of parietal cells in the isthmus–neck region was examined. Pretreatment with famotidine resulted in a slight increase of macroscopically visible gastric lesions in response to HCl. While the extent of total histologic damage was not modified, the antisecretory dose significantly reduced only lesions deep within the mucosa. Famotidine alone determined the dose-dependent occurrence of a distinct parietal cell morphological state, suggestive of inhibition of the secretory system. A causal link between the protective effect on the region where parietal cells are located, the percentage of cells shifting to the inhibited morphological state, and the inhibitory effect on acid secretion is proposed.     

Stereologic Investigations of Human Gastric Mucosa: II. Oxyntic Mucosa from Patients with Zollinger-Ellison Syndrome

Biopsy specimens from the oxyntic mucosa were obtained on 210 occasions from 76 patients with the Zollinger-Ellison syndrome (ZES) before and during omeprazole treatment. One-micrometer sections were examined by light microscopy, and in 5% linear hyperplasia of endocrine cells was observed. Morphometry was carried out in 91 of the specimens and showed a significant increase of the mean endocrine cell density in comparison with both young, healthy subjects and patients suffering from active peptic ulcer disease (PUD). No metaplasia, dysplasia, or neoplasia was detected in patients with ZES, and the mean mucosal thickness and parietal cell density remained normal. The parietal cells often displayed endosome-like structures, and occasionally there were Ungulate cytoplasmic projections into the gland lumen. Electron microscopic morphometry was carried out in specimens from nine patients with ZES and did not show any significant differences in the parietal cells in comparison with healthy subjects.     

Morphology and Function of the Parietal Cells after Proximal Selective Vagotomy in Duodenal Ulcer Patients

The effects of proximal selective vagotomy (PSV) on parietal cell morphology and the degree of gastric inflammation were investigated and correlated with changes in gastric acid secretion and serum gastrin concentrations in 17 duodenal ulcer patients. Endoscopy, acid secretion tests, and blood sampling were performed preoperatively and 2 months, 1 year, and 3 years postoperatively. The mucosal biopsy specimens obtained at endoscopy were analyzed both light-and electron-microscopically. Five healthy persons also underwent gastroscopy and biopsy for comparison. Preoperatively, the duodenal ulcer patients differed significantly from this control group. 33% of whose parietal cells appeared ‘secretory’; the corresponding figure for the duodenal ulcer patients was 47%. Two months after the operation the number of secretory parietal cells had fallen to 30%, after which the percentage increased slightly again to 35% 3 years after PSV. A similar phenomenon was observed in the acid secretion capacities, which were maximally depressed 2 months postoperatively and recovered slightly but significantly during the 3-year follow-up period. There was a significant increase in the degree of gastric inflammation after the operation.     

胃痛灵对大鼠胃粘膜血流量及脾虚大鼠模型的影响

为深入探讨胃癌灵保护胃粘膜的作用机制，研究了胃痛灵（WTL）对无水乙醇损伤大鼠胃粘膜血流量（GMBF）、脾虚大鼠D-木糖吸收率、胃壁结合粘液量以及胃酸分泌和胃蛋白酶活性的影响。结果显示WTL能够明显增加大鼠GMBF（P＜0．05）、胃壁结合粘液量（P＜0．05），提高脾虚大鼠D-木糖吸收率（P＜0．05），增强胃粘膜防御机能，但对脾虚大鼠胃酸的分泌和胃蛋白酶活性均无明显影响。在体外也无中和胃酸的能力。     

Effect of Helicobacter pylori on Parietal Cell Sensitivity to Pentagastrin in Duodenal Ulcer Subjects

Chittajallu RS, Howie CA, McColl KEL. Effect of Helicobacter pylori on parietal cell sensitivity to pentagastrin in duodenal ulcer subjects. Scand J Gastroenterol 1992;27:857-862.

We have investigated the possibility that hypergastrinaemia in chronic Helicobacter pylori infection is a compensatory response to reduced parietal cell sensitivity to gastrin. The acid response to 45-min infusions of pentagastrin at sequential doses (mg/kg/h) of 0, 0.031, 0.062, 0.124, and 0.6 was compared before and 1 month after eradication of H. pylori in eight duodenal ulcer patients. The median acid outputs (mmol/h) with the respective infusions were 5.0, 7.5, 26.5, 30.8, and 37.0 when H. pylori-positive and similar at 4.5, 7.1, 22.7, 28, and 31.5 when H. pylori-negative. The median estimated dose of pentagastrin required to produce 50% maximal response (D₅₀) was similar before (0.060 mg/kg/h) and after (0.057 mg/kg/h) eradication of H. pylori. The median estimated maximal response to pentagastrin (mmol/h) was also similar before (39.2) and after (32.3) treatment. The median basal gastrin concentration was 48 ng/1 (range, 22-77) before treatment and fell to 33 ng/1 (range, 8-37) after eradication of H. pylori (p = 0.03). These findings show that the parietal cell sensitivity to pentagastrin is unaffected by chronic H. pylori infection in duodenal ulcer subjects and that the hypergastrinaemia cannot be attributed to the bacterium inhibiting parietal cell function.     

实验脾虚证胃窦及十二指肠粘膜G、D细胞的变化及意义

目的：探讨Ｇ细胞（分泌胃泌素）、Ｄ细胞（分泌生长抑素）与脾虚证发生的关系。方法：应用抗－胃泌素、抗－生长抑素的多克隆抗体和免疫组织化学技术标记胃窦、十二指肠粘膜Ｇ、Ｄ细胞,运用医学图像分析系统（ＭＩＰＳ）对Ｇ、Ｄ细胞进行定量分析,并与四君子汤组对照。结果：脾虚时Ｇ、Ｄ细胞数均减少,Ｄ细胞面积缩小,Ｇ细胞灰度值增高,Ｇ／Ｄ细胞数和细胞面积比值均增高。经四君子汤预防和治疗的脾虚大鼠,Ｇ、Ｄ细胞数有所增加,Ｄ细胞面积明显增大,Ｇ细胞灰度值、Ｇ／Ｄ细胞数和细胞面积比值均接近或略低于正常。脾虚自然恢复大鼠也有一定程度的改善,但与脾虚四君子汤预防和治疗大鼠相比有显著性差异。结论：研究结果从形态学上揭示Ｄ细胞分泌ＳＳＴ亢进、Ｇ细胞释放Ｇａｓ不足、Ｇ／Ｄ细胞比例失调,是导致脾虚证胃肠功能障碍的一个重要病理机制。     

脾虚证大鼠组织中胃泌素及生长抑素含量的变化及意义

为探讨胃泌素（Gas）及生长抑素（SST）与脾虚证发生的关系，观察了实验脾虚证发生过程中组织Gas、SST含量的变化，并用四君子汤反证。结果脾虚时组织中Gas含量低下，SST含量增高。经四君子汤预防和治疗的脾虚大鼠，Gas及SST水平紊乱的状态得以明显的改善．明显优于脾虚自然恢复大鼠。结果初步表明，组织中Gas、SST水平紊乱是导致脾失健运的主要原因之一。