Konturek J W, Hengst K, Konturek S J, Sito E, Stachura J, Domschke W
Department of Medicine B, University of Münster, Germany.
Am J Gastroenterol. 1998 Dec;93(12):2385-90. doi: 10.1111/j.1572-0241.1998.00692.x.
Cholecystokinin (CCK) is able to protect gastric mucosa against acute injury in experimental animals but little is known about the role of this hormone in maintaining mucosal integrity in humans. This double-blind, placebo controlled study was performed in 16 healthy volunteers. It describes the effects of CCK-8 infused intravenously (i.v.) at physiological doses and endogenous CCK released by intraduodenal (i.d.) oleate on gastric mucosal damage, as brought about by ethanol without or with pretreatment with loxiglumide, a selective CCK-A receptor antagonist.
CCK-8 was infused i.v. 30 min before and throughout the study or i.d. oleate was instilled through a separate duodenal tube. Thirty minutes after the start of i.v. infusion of CCK or i.d. oleate instillation, 100 ml of 50% ethanol spray was applied to the gastric mucosa using an endoscope. Gastroscopy was performed and mucosal lesions were quantified using modified Lanza score. Gastric biopsies were taken from oxyntic mucosa for histological evaluation and gastric content was aspirated for radioimmunoassay of somatostatin.
In placebo-treated subjects ethanol caused endoscopic damage, with an average score of 2.8+/-0.2. Histologically, a widespread disruption of surface epithelium and deep hemorrhagic necrotic lesions were observed. Pretreatment with CCK or i.d. oleate markedly reduced the endoscopic lesion score to 0.7+/-0.1 and 0.3+/-0.1, respectively, and in both cases this reduction was accompanied by a significant rise in plasma CCK. Histologically, surface epithelium was still disrupted but deep necrotic lesions were absent. Gastric content collected before and after CCK or oleate showed a several-fold increase of luminally released somatostatin.
Pretreatment with loxiglumide abolished the protective effects of i.v. CCK-8 and i.d. oleate on mucosal lesions induced by ethanol and prevented the rise in intragastric somatostatin, but failed to affect the increments in plasma CCK. Endogenous CCK plays a physiological role in the maintenance of mucosal integrity. This occurs through activation of CCK-A receptors and is associated with an increased gastric luminal release of somatostatin.
胆囊收缩素（CCK）能够保护实验动物的胃黏膜免受急性损伤，但关于这种激素在维持人类黏膜完整性中的作用却知之甚少。本双盲、安慰剂对照研究在16名健康志愿者中进行。它描述了生理剂量静脉注射（i.v.）CCK-8以及十二指肠内（i.d.）注入油酸盐释放的内源性CCK对乙醇所致胃黏膜损伤的影响，其中乙醇所致胃黏膜损伤有无预先使用选择性CCK-A受体拮抗剂洛西肽胺处理。
在研究前30分钟及整个研究过程中静脉注射CCK-8，或通过单独的十二指肠管注入十二指肠内油酸盐。静脉注射CCK或十二指肠内注入油酸盐开始30分钟后，使用内窥镜将100毫升50%乙醇喷雾应用于胃黏膜。进行胃镜检查，并使用改良的兰扎评分对黏膜病变进行量化。从胃体黏膜取胃活检组织进行组织学评估，并抽取胃内容物进行生长抑素的放射免疫测定。
在安慰剂治疗的受试者中，乙醇导致内镜下损伤，平均评分为2.8±0.2。组织学上，观察到表面上皮广泛破坏和深部出血性坏死病变。预先使用CCK或十二指肠内注入油酸盐可使内镜病变评分显著降低至分别为0.7±0.1和0.3±0.1，并且在这两种情况下，这种降低都伴随着血浆CCK的显著升高。组织学上，表面上皮仍有破坏，但无深部坏死病变。在CCK或油酸盐处理前后收集的胃内容物显示，腔内释放的生长抑素增加了数倍。
预先使用洛西肽胺消除了静脉注射CCK-8和十二指肠内注入油酸盐对乙醇诱导的黏膜病变的保护作用，并阻止了胃内生长抑素的升高，但未能影响血浆CCK的升高。内源性CCK在维持黏膜完整性中发挥生理作用。这是通过激活CCK-A受体发生的，并且与胃腔内生长抑素释放增加有关。
