Taylor I L, Sells R A, McConnell R B, Dockray G J
Gut. 1980 Dec;21(12):1062-7. doi: 10.1136/gut.21.12.1062.
The realisation that circulating gastrin is heterogeneous necessitates a reappraisal of gastrin's role in the increased incidence of duodenal ulcer disease that occurs in chronic renal failure. Radioimmunoassays employing region-specific antisera have been used to examine renal and extrarenal factors controlling serum gastrin concentration in patients with chronic renal failure. The present study has shown that basal serum gastrin concentrations measured with a carboxyl-terminal specific antibody were significantly higher in eight patients with chronic renal failure treated by dietary restriction (388+/-196 pM) than in 14 patients with chronic renal failure treated by haemodialysis (28.7+/-4.6 pM). However, basal gastrin concentrations in both groups of patients were significantly higher than in 25 normal subjects (12.3+/-1.8 pM) and showed significant negative correlations with maximal gastric acid secretion (p < 0.01). Markedly raised basal gastrin concentrations were observed only in chronic renal failure patients who were also achlorhydric. Although the peak postprandial increment in big gastrin concentration in 11 chronic renal failure patients (34.0+/-7.5 pM) was significantly greater (p < 0.05) than in 25 normal subjects (19.5+/-4.6 pM), the little gastrin responses were not significantly different. In addition, clearance of exogenous little gastrin was similar in four chronic failure patients (clearance half time: 8.1+/-0.7 min) and four normal subjects (clearance half time: 6.5+/-1.2 min). These studies suggest that the human kidney is unimportant in the metabolism of little gastrin. As circulating little gastrin is six times more potent than big gastrin in stimulating acid secretion, these studies suggest that the raised gastrin concentrations observed in patients with chronic renal failure have little significance in terms of their increased incidence of duodenal ulcer disease.
认识到循环胃泌素具有异质性，就需要重新评估胃泌素在慢性肾衰竭时十二指肠溃疡疾病发病率增加中所起的作用。采用区域特异性抗血清的放射免疫分析法已被用于研究控制慢性肾衰竭患者血清胃泌素浓度的肾脏和肾外因素。本研究表明，用羧基末端特异性抗体测得的8例接受饮食限制治疗的慢性肾衰竭患者的基础血清胃泌素浓度（388±196 pM）显著高于14例接受血液透析治疗的慢性肾衰竭患者（28.7±4.6 pM）。然而，两组患者的基础胃泌素浓度均显著高于25名正常受试者（12.3±1.8 pM），且与最大胃酸分泌呈显著负相关（p<0.01）。仅在同时伴有胃酸缺乏的慢性肾衰竭患者中观察到基础胃泌素浓度显著升高。尽管11例慢性肾衰竭患者餐后大胃泌素浓度的峰值增量（34.0±7.5 pM）显著高于25名正常受试者（19.5±4.6 pM）（p<0.05），但小胃泌素的反应无显著差异。此外，4例慢性肾衰竭患者（清除半衰期：8.1±0.7分钟）和4名正常受试者（清除半衰期：6.5±1.2分钟）对外源性小胃泌素的清除情况相似。这些研究表明，人肾在小胃泌素的代谢中作用不大。由于循环中的小胃泌素在刺激胃酸分泌方面的效力比大胃泌素高6倍，这些研究表明，慢性肾衰竭患者中观察到的胃泌素浓度升高对其十二指肠溃疡疾病发病率增加的意义不大。
