硒对大鼠胃癌的作用及对其内分泌细胞的影响

目的　探讨硒在机体自然抗肿瘤发生过程中的作用。方法　给断乳雄性 Wistar大鼠 MNNG(N甲基 - N -硝基 - N亚硝胍 2 0 mg/kg)灌胃 ,每天一次 ,连续 1 0 d,以诱导大鼠胃粘膜异倍体形成 (大鼠胃癌模型形成 )。第 2 5wk时 ,用流式细胞仪测定硒对大鼠胃幽门粘膜异倍体形成的影响 ,用免疫组织化学 ABC法观察大鼠胃粘膜异倍体形成过程中 ,其胃的胃泌素细胞 (G细胞 )、生长抑素细胞 (SS细胞 )、5-羟色胺细胞 (5- HT细胞 )的免疫组织化学变化 ,并对以上结果进行定性、定位、定量分析以及统计学处理。结果　 1 .硒能抑制 MNNG所致大鼠胃粘膜细胞异倍体的形成。 2 .实验对照组与正常对照组比较 ,大鼠胃粘膜胃泌素细胞的免疫组织化学反应明显增强 (P<0 .0 1 ) ,SS细胞、5- HT细胞也有增强的趋势 (P>0 .0 5)。 3.加硒各组与实验对照组比较 ,大鼠胃粘膜胃泌素细胞的免疫组织化学反应明显减弱 (P<0 .0 1 ) ,SS细胞、5- HT细胞也有减弱的趋势 (P>0 .0 5)。结论　内分泌细胞可能与 MNNG所致大鼠胃粘膜细胞异倍体的形成和发展有关 ;硒可能对大鼠胃内分泌细胞的功能有一定影响     

Effect of liquid diet on nude mouse gastrointestinal tract

The nude (athymic) mouse is currently used to study the effect of gastrin on cancer xenografts. We sought to develop a hypogastrinemia nude mouse model for use in evaluating the effect of hypogastrinemia on such xenografts. Thirty-six non-tumor-bearing nude mice were studied. Eighteen received a nutritionally complete liquid diet; eighteen received standard chow. Six mice from each group were weighed and killed (nonfasting) on days 2, 8, and 15. Mean serum gastrin levels (+/- SEM) for the control group were 118.7 +/- 7.5, 118.7 +/- 8.7, and 118.0 +/- 7.5 pg/ml on days 2, 8, and 15, respectively. Serum gastrin levels for the liquid diet group significantly decreased to 87.0 +/- 7.6, 88.0 +/- 9.7, and 66.7 +/- 9.6 pg/ml on the same days. Animals in both groups gained weight normally; there were no significant weight differences between the two groups at any point. No histological abnormalities were seen in stomach, small intestine, colon, cecum, liver, pancreas, spleen or kidney. However, the liquid diet group showed atrophic changes in colon: significant reductions in colon weight and RNA content on days 8 and 15, and significant reduction in colon protein content on day 8. This model of hypogastrinemia is reliable and inexpensive. The nonsurgical nature of the preparation allows excellent survival in this immunodeficient animal.     

慢性萎缩性胃炎胃泌素细胞的数量和形态学改变(免疫组化及超微结构研究)

本文用免疫组化及透射电镜观察浅表性及慢性萎缩性胃炎的G细胞数量及形态变化。胃窦部粘膜68例,其中正常胃粘膜12例,浅表性胃炎6例,慢性萎缩性胃炎50例。浅表性胃炎及慢性萎缩性胃炎的G细胞数均比正常者减少,特别是后者。随着慢性萎缩性胃炎病变的加重,G细胞数也随之减少。慢性萎缩性胃炎G细胞分布不均,肠化区无G细胞,腺上皮不典型增生区G细胞明显减少。电镜观察详细地描述了正常胃粘膜和慢性萎缩性胃炎G细胞的形态。讨论了慢性萎缩性胃炎G细,胞数量减少和分布不均的原因,及其与胃癌的关系。     

Effect of 16, 16-dimethyl prostaglandin E2 on small intestinal mucosa in suckling rats

Suckling rats were treated every 8 h by intragastric instillation of 16,16-dimethyl prostaglandin E2 (PG) in a dose of 25 micrograms kg-1 (PG25), or 100 micrograms kg-1 (PG100), or saline from postnatal day 7-11. PG increased small intestinal villus length and crypt depth, most markedly in the duodenum, leading to a mucosal height of 543 +/- 24 microns after saline, 670 +/- 26 microns after PG25 and 823 +/- 40 microns after PG100. In the proximal small bowel, PG100 raised the mean activities of sucrase by 439%, maltase by 98%, trehalase by 584%, lactase by 58% and alkaline phosphatase by 76%. In the distal small intestine, only sucrase and trehalase activities were stimulated whereas other enzymes were depressed. PG25 caused similar but less pronounced changes of enzyme activities. Eight hours after both the last PG25 and the last PG100 dose, plasma gastrin and corticosterone levels were decreased while thyroxine remained unchanged. The effect of a single dose of 100 micrograms kg-1 PG or saline was also tested on 5- and 11-day-old rats; they were killed 16 h after PG administration. An increase in villus length occurred along the entire small intestine of rats treated on day 5, and also in the ileum of rats treated on day 11. In the proximal intestine, maltase and trehalase were stimulated after early and late treatment and, in addition, sucrase and lactase after late treatment. Serum corticosterone levels were found to be significantly higher 2-6 h after PG100 than in the controls and then decreased gradually.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biological effects and receptor binding affinities of new pseudononapeptide bombesin/GRP receptor antagonists with N-terminal d-Trp or d-Tpi

In an attempt to produce more powerful (effective) bombesin/GRP receptor antagonists, the d forms of Trp or Trp analog (Tpi) were introduced at position 6 in two pseudononapeptides, Leu¹³Ψ (CH₂NH)Leu¹⁴-bombesin(6-14) and Leu¹³Ψ(CH₂NH)Phe¹⁴ -bombesin (6-14). These antagonists were tested for their ability to inhibit basal and gastrin releasing peptide (GRP) (14-27)-induced amylase release from rat pancreatic acini in a superfusion assay. They were also assessed for the inhibition of ¹²⁵I-Tyr⁴ -bombesin binding to Swiss 3T3 and small cell lung carcinoma cell line H-345 and the mitogenic response of Swiss 3T3 cells induced by GRP(14-27). The peptides, when given alone, did not stimulate amylase secretion, but were able to inhibit gastrin releasing peptide (14-27)-induced amylase release. All of the antagonists showed strong binding affinities for Swiss 3T3 and H-345 cells and suppressed the GRP(14-27)-induced increase of [³H]thymidine incorporation into DNA of Swiss 3T3 cells at nanomolar concentrations. Antagonist d -Tpi⁶,Leu¹³Ψ (CH₂NH)Leu¹⁴-bombesin (6-14)(RC-3095) was slightly more potent in these assays than d -Trp⁶,Leu¹³Ψ (CH₂NH)Leu¹⁴-bombesin (6-14)(RC-3125). Nevertheless, d -Trp⁶ Leu¹³Ψ (CH₂NH)Phe¹⁴-bombesin (6-14) showed the highest binding affinity for Swiss 3T3 and H345 cells and it was the most potent inhibitor of GRP(14-27)-induced amylase secretion. This antagonist RC-3420 was particularly effective in inhibiting the growth of Swiss 3T3 cells, exhibiting an IC₅₀ value less than 1 nm . Our work indicated that the substitution of d -Trp and d -Tpi at position 6 of the pseudononapeptide bombesin analogs (Ψ^13-14), in which the Met¹⁴ residue is replaced by Leu or Phe, results in potent bombesin/GRP antagonists with improved in vivo activity.     

Visualisation of the gastrin receptor within rat mucosa using a biotinylated gastrin antagonist

We have previously demonstrated that the peptide Boc-l -Trp-l -Leu-β-Ala is a potent and specific antagonist of pentagastrin-stimulated acid secretion in both the rat and the dog. Using conventional solution phase methodology, the analogue biotinyl-l -Trp-l -Leu-β-Ala was prepared in reasonable yield and purity and applied to cryostat sections of rat intestinal and other tissues. The sections were exposed to 5–10 μg of peptide and the bound analogue was visualised using streptavidin-fluorescein. The binding of the analogue was demonstrated in sections from fundus, duodenum, ileum, colon, and lung. However, the analogue failed to bind to tissue from the pancreas, heart, kidney, or liver. The binding of the probe was greatly reduced or completely inhibited by preincubation with Boc-l -Trp-l -Leu-β-Ala, pentagastrin, or gastrin 1–17. The distribution of the cells recognised by the probe was consistent with the distribution of histamine-containing enterochromaffin-like cells. The results of this study may have some bearing on current theories of the mechanism of gastrin-stimulated acid release.     

THE VAGUS AND NEUROTENSIN RELEASE IN DUODENAL ULCER—CLINICAL AND EXPERIMENTAL STUDIES

Although meal-stimulated neurotensin release from the small intestine is inhibited by cholinergic blockade, it is uncertain whether this cholinergic mechanism involves the vagus. This study examines me role of the vagus in neurotensin release by first determining the effect of vagotomy on meal-stimulated plasma neurotensin in man and second, the effect on plasma neurotensin of electrical stimulation of the vagus in sheep. Six volunteers were studied 6–8 weeks after truncal vagotomy and pyloroplasty. Basal plasma neurotensin at 32(15–67) pmol/l (median, range) was greater than in normal controls at 17 (9–52) pmol/1 (p < 0.05). Following a standard meal, plasma neurotensin rose significantly (p < 0.05), but similarly in both post-vagotomy and control groups to maxima of 74 (43–76) pmol/l and 52 (35–65) pmol/l, respectively. Basal plasma neurotensin in the six sheep was below the detection limit of the assay and remained undetectable during electrical stimulation of the vagus. Significant rises in plasma pancreatic polypeptide and gastrin confirmed the efficacy of the electrical stimulation. It is concluded that although the vagus might have a tonic inhibitory effect on basal plasma neurotensin, meal-stimulated neurotensin release is vagally independent. The inhibitory cholinergic influence on meal-stimulated release is most likely therefore to be mediated by cholinergic nerves of the enteric nervous system.     

测定肺癌病人血清胃泌素水平的临床意义

本实验用放射免疫法测定70例肺癌手术前、后血清胃泌索水平的动态变化,并以40例非癌胸疾病人和151例正常人作对照。结果表明:肺癌病人血清胃泌素水平明显高于非癌胸疾病人和正常人(p<0.01)。胃泌素水平与肺癌病期、原发肿瘤大小、淋巴结转移,以及病理类型有明显关系。行根治性肿瘤切除术后,胃泌素水平逐渐降低,术后14天可降至正常水平。术后14天血清胃泌素能降至正常者,预后良好;反之,则预后不良。上述结果表明肺癌病人血清含有高浓度胃泌素,手术前后测定血清胃泌素有助于胸部良性和恶性病变的诊断,以及评价肺癌病人预后。肺癌病人血清胃泌素增高的原因可能是肺癌细胞能释放胃泌素所致。     

Ratio between serum IL-8 and pepsinogen A/C: a marker for atrophic body gastritis

BACKGROUND AND AIMS: Elevated serum gastrin and a low pepsinogen A/C ratio are well-recognized markers for atrophic body gastritis (ABG). We have shown that the presence of body atrophy is also associated with elevated serum pro-inflammatory cytokines. This study tested the hypothesis that serum cytokines provide additional information to gastrin and pepsinogens in screening for ABG. METHODS: Two hundred and twenty-six consecutive patients were investigated on referral for upper gastrointestinal endoscopy: 150 were patients with gastro-oesophageal reflux disease, receiving acid inhibitory medication either with proton pump inhibitors (n = 113) or with histamine2-receptor antagonists (n = 37), and 76 were nontreated controls, who had normal endoscopic findings. Gastric mucosal biopsies were sampled for histological examination (Sydney classification). Serum samples were analyzed for gastrin, chromogranin A (CgA), and pepsinogens A and C by RIA, and for the interleukins (IL)-1beta, IL-6, and IL-8 by ELISA. RESULTS: Subjects with ABG had significantly higher serum gastrin (P < 0.01) and serum CgA (P < 0.01) levels and significantly lower pepsinogen A/C ratios (P < 0.001) than those without ABG. Additionally, serum IL-1beta, IL-6 and, especially, IL-8 levels were significantly higher in the subjects with than in those without ABG (P < 0.0001, for all cytokines). To optimize the detection of body atrophy we defined the ABG index: the ratio between the simultaneously measured IL-8 and pepsinogen A/C. The area under the ROC curve for the ABG index was significantly greater than that for serum gastrin and for serum pepsinogen A/C alone (0.91 +/- 0.029 vs. 0.72 +/- 0.042, and vs. 0.83 +/- 0.031, P = 0.018 and P = 0.049). Using the ABG index at a cut-off value of 1.8 pg mL-1, 91% of the cases were classified correctly. CONCLUSIONS: The ratio between serum IL-8 and pepsinogen A/C accurately predicts the presence of ABG. We therefore propose the ABG index as a noninvasive screening test for ABG in population-based studies.     

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。