肝硬化患者血浆中的胆囊收缩素及其前体

Plasma cholecystokinin and its precursors in hepatic cirrhosis.

作者信息

Paloheimo L I, Clemmesen O, Dalhoff K, Rehfeld J F

机构信息

Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Denmark.

出版信息

J Hepatol. 1997 Aug;27(2):299-305. doi: 10.1016/s0168-8278(97)80175-4.

DOI:10.1016/s0168-8278(97)80175-4

PMID:9288604

Abstract

BACKGROUND/AIMS: The liver influences the metabolism of several peptide hormones. The metabolic effect may, however, change considerably by diseases in the liver. This study examined whether hepatic cirrhosis influences the occurrence and concentrations of procholecystokinin (proCCK) and its products in plasma.

METHODS

The sum of proCCK and its products (both processing intermediates and bioactive fragments) in plasma were measured by a recently developed "processing-independent analysis". Bioactive forms of CCK in plasma were measured using a highly specific radioimmunoassay directed against the C-terminal epitope of CCK.

RESULTS

In plasma from patients with primary biliary cirrhosis the basal concentration of the total proCCK product was increased. Moreover, a mixed meal increased plasma concentrations of both bioactive CCK (i.e. carboxyamidated an 0-sulfated CCK peptides) and the total proCCK product in primary biliary cirrhosis. In contrast, plasma concentrations of bioactive CCK and the total proCCK product were normal in patients with alcoholic liver cirrhosis-both pre- or postprandially. The fraction of bioactive CCK in plasma from patients with both biliary and alcoholic cirrhosis was also normal. Hence, in primary biliary cirrhosis, alcoholic cirrhosis and in controls, respectively, bioactive CCK constituted 15%, 15% and 17% of the total proCCK product in the basal state; 70%, 58% and 53% 30 min after and 48%, 56% and 51% 90 min after the meal. As shown by gel chromatography, plasma from patients with primary biliary cirrhosis and controls sampled 30 min after a meal contained CCK-33, -22 and -8-like peptides. In addition, plasma contained non-amidated (approximately non-bioactive) proCCK products corresponding in size to CCK-83, -58 and -33. Ninety minutes after a meal, CCK-8 predominated in plasma from patients with primary biliary cirrhosis, whereas plasma from controls displayed a CCK profile similar to that obtained 30 min post-prandially.

CONCLUSIONS

The results show that CCK-8 is metabolized at a slower rate in patients with primary biliary cirrhosis.

摘要

背景/目的：肝脏影响多种肽类激素的代谢。然而，肝脏疾病可能会使这种代谢效应发生显著变化。本研究检测了肝硬化是否会影响血浆中前胆囊收缩素（proCCK）及其产物的产生和浓度。

方法

采用最近开发的“独立于加工过程的分析方法”测定血浆中proCCK及其产物（包括加工中间体和生物活性片段）的总和。使用针对CCK C末端表位的高度特异性放射免疫分析法测定血浆中CCK的生物活性形式。

结果

在原发性胆汁性肝硬化患者的血浆中，总proCCK产物的基础浓度升高。此外，一顿混合餐可使原发性胆汁性肝硬化患者血浆中生物活性CCK（即酰胺化和0-硫酸化CCK肽）和总proCCK产物的浓度均升高。相比之下，酒精性肝硬化患者餐前和餐后血浆中生物活性CCK和总proCCK产物的浓度均正常。胆汁性和酒精性肝硬化患者血浆中生物活性CCK的比例也正常。因此，在原发性胆汁性肝硬化、酒精性肝硬化患者及对照组中，基础状态下生物活性CCK分别占总proCCK产物的15%、15%和17%；餐后30分钟分别占70%、58%和53%；餐后90分钟分别占48%、56%和51%。凝胶色谱分析显示，原发性胆汁性肝硬化患者和餐后30分钟取样的对照组血浆中含有CCK-33、-22和-8样肽。此外，血浆中还含有大小与CCK-83、-58和-33相对应的未酰胺化（近似无生物活性）proCCK产物。餐后90分钟，原发性胆汁性肝硬化患者血浆中CCK-8占主导，而对照组血浆中的CCK谱与餐后30分钟时相似。