Ohlsson B, Axelson J, Rehfeld J F, Ihse I
Department of Surgery, University Hospital, Lund, Sweden.
Eur Surg Res. 1996 Jul-Aug;28(4):299-305. doi: 10.1159/000129470.
Cholecystokinin (CCK) is a potent stimulus of pancreatic enzyme secretion and growth and is known to influence the flow of biliary secretions. It has also been suggested as a trophic stimulus of the biliary tract and liver, but confirmatory studies are lacking. The aim of the present experiment was to study the effects on the rat liver and biliary tract of long-term stimulation of CCK-8S and the CCK-A receptor antagonist devazepide, respectively. Sprague-Dawley male rats had an infusion of sulfated CCK-8, devazepide or sodium chloride by subcutaneously implanted osmotic minipumps. The animals were sacrified 36 h and 3, 7 or 28 days after the start of infusion, and all had an injection of tritiated thymidine (1 mCi/kg) intraperitoneally 1 h prior to death. The liver was dissected out, weighed and processed for its content of protein, DNA and water. After autoradiography, histologic samples were examined for labeled hepatocytes and bile duct epithelium. Devazepide caused an increase in liver protein content from 36 h on. After 3 days labeling index of hepatocytes and liver DNA concentration were increased. On day 7, induced cell proliferation was also seen in the bile duct epithelium, and the increase in liver DNA content and concentration was now more pronounced and persisted throughout the study. After 28 days devazepide also induced increased crude and relative liver weight. A transient reduction in liver weight and liver protein content and concentration was seen after 7 days of CCK-8S infusion. There were no changes of the labeling index of hepatocytes or bile duct epithelial cells or in liver DNA content in the rats receiving CCK-8S infusion. Devazepide induced hyperplastic changes in both the liver and the biliary tract, probably by interfering with the bile secretion, whereas CCK-8S did not exert any similar effects. The results do not support CCK as a hepatotrophic factor.
胆囊收缩素（CCK）是胰腺酶分泌和生长的强效刺激物，并且已知会影响胆汁分泌的流量。也有人提出它是胆道和肝脏的营养刺激物，但缺乏确证性研究。本实验的目的是分别研究长期刺激CCK-8S和CCK-A受体拮抗剂地伐西匹对大鼠肝脏和胆道的影响。将硫酸化CCK-8、地伐西匹或氯化钠通过皮下植入的渗透微型泵输注到Sprague-Dawley雄性大鼠体内。在输注开始后36小时以及3、7或28天处死动物，并且所有动物在死亡前1小时腹腔注射氚标记的胸腺嘧啶核苷（1毫居里/千克）。取出肝脏，称重并对其蛋白质、DNA和水的含量进行处理。放射自显影后，检查组织学样本中标记的肝细胞和胆管上皮。地伐西匹从36小时起导致肝脏蛋白质含量增加。3天后，肝细胞的标记指数和肝脏DNA浓度增加。在第7天，胆管上皮也出现诱导性细胞增殖，并且肝脏DNA含量和浓度的增加现在更加明显并且在整个研究过程中持续存在。28天后，地伐西匹还诱导肝脏粗重和相对重量增加。输注CCK-8S 7天后，观察到肝脏重量、肝脏蛋白质含量和浓度出现短暂下降。接受CCK-8S输注的大鼠中，肝细胞或胆管上皮细胞的标记指数以及肝脏DNA含量没有变化。地伐西匹可能通过干扰胆汁分泌诱导肝脏和胆道的增生性变化，而CCK-8S没有发挥任何类似作用。结果不支持CCK作为一种肝营养因子。
