地伐西匹和CCK-8S对完整及切除肝脏大鼠的影响评估。

An evaluation of the influence of devazepide and CCK-8S on the intact and resected rat liver.

作者信息

Ohlsson B, Rehfeld J F, Axelson J

机构信息

Department of Surgery, University Hospital, Lund, Sweden.

出版信息

Eur Surg Res. 1998;30(6):378-84. doi: 10.1159/000008602.

DOI:10.1159/000008602

PMID:9838229

Abstract

BACKGROUND

Recently, it has been shown that infusion of the CCK-A receptor antagonist devazepide induced proliferation of hepatocytes and bile duct epithelium in the rat liver. The aim of this study was to further evaluate the influence of devazepide and sulfated cholecystokinin-8 (CCK-8S) on the intact rat liver and rat liver after resection.

METHODS

In the first experiment, either saline or devazepide was injected subcutaneously twice daily to rats for 18 and 36 h and 3 and 7 days. In the second experiment, a 70% liver resection was followed by infusion of either DMSO, devazepide, saline or CCK-8S for 2 or 7 days. Prior to sacrifice, all rats received 1 mCi/kg of tritiated thymidine intraperitoneally. The liver was excised and the contents of protein, DNA and water and incorporation of tritiated thymidine were measured.

RESULTS

Intermittent injections of devazepide increased the liver protein content after 36 h, followed by a decrease after 7 days. The weight, DNA content or cell proliferation was not affected. Two days after liver resection hyperCCKemia was evoked, which was less prominent after 7 days. Devazepide lowered the plasma concentration of CCK, while the infusion of CCK-8S resulted in extremely high concentrations at both time points. The DNA synthesis measured by thymidine incorporation was increased by devazepide on day 2, whereas the weight or protein and DNA contents of the liver were not influenced. CCK-8S infusion decreased the body and liver weight throughout the study, and the protein and DNA contents after 7 days.

CONCLUSIONS

Intermittent devazepide treatment did not affect the intact liver. Devazepide increased the DNA synthesis 2 days after liver resection but was without other influences on the liver regeneration. CCK-8S induced decreased body weight with ensuing negative effects on the liver regeneration. Neither devazepide nor CCK seem to be of any therapeutic use after liver resection or liver failure.

摘要

背景

最近研究表明，注射胆囊收缩素A（CCK-A）受体拮抗剂地伐西匹可诱导大鼠肝脏的肝细胞和胆管上皮细胞增殖。本研究旨在进一步评估地伐西匹和硫酸化胆囊收缩素-8（CCK-8S）对正常大鼠肝脏及肝切除术后大鼠肝脏的影响。

方法

在第一个实验中，分别向大鼠皮下注射生理盐水或地伐西匹，每日两次，持续18小时、36小时、3天以及7天。在第二个实验中，先进行70%的肝切除术，然后分别向大鼠输注二甲基亚砜（DMSO）、地伐西匹、生理盐水或CCK-8S，持续2天或7天。在处死大鼠前，所有大鼠均腹腔注射1毫居里/千克的氚标记胸腺嘧啶核苷。切除肝脏后，测量肝脏的蛋白质、DNA和水分含量以及氚标记胸腺嘧啶核苷的掺入量。

结果

间歇性注射地伐西匹36小时后肝脏蛋白质含量增加，7天后则下降。肝脏重量、DNA含量或细胞增殖未受影响。肝切除术后两天引发了高CCK血症，7天后这种情况不太明显。地伐西匹降低了CCK的血浆浓度，而输注CCK-8S在两个时间点均导致极高的浓度。在第2天，通过胸腺嘧啶核苷掺入法测得的DNA合成量因地伐西匹而增加，然而肝脏重量、蛋白质和DNA含量未受影响。在整个研究过程中，输注CCK-8S均降低了大鼠体重和肝脏重量，7天后还降低了蛋白质和DNA含量。