胆囊收缩素对IL－1β损伤的胰岛β细胞功能的保护作用及其机制分析

PROTECTIVE EFFECT OF CHOLECYSTOKIN OCTAPEPTIDE ON INTERLEUKIN 1β INJURED PANCREATIC ISLETS IN NEWBORN RATS AND ITS MECHANISM

本实验在分离培养的新生大鼠胰岛上，观察了胆囊收缩素（ＣＣＫ－８）对白细胞介素－１β（ＩＬ—１β）损伤的胰岛β细胞功能的影响。并就其机制进行初步分析。结果表明：（１）ＩＬ—１β（５，１０，２０Ｕ／ｍｌ）能抑制葡萄糖（２０ｍｍｏｌ／Ｌ）刺激的胰岛素分泌，其抑制作用具有量效关系，抑制率分别为５３．４％，６０．５％和７０．７％。（２）ＣＣＫ－８对ＩＬ－１损伤的胰岛β细胞的功能具有保护作用。预防性地给予ＣＣＫ－８（１０￣（－１０），１０￣（－９），１０￣（－８），１０￣（－７）ｍｏｌ／Ｌ）能防止ＩＬ－１β对葡萄糖刺激的胰岛素分泌的抑制作用。治疗性地给予ＣＣＫ－８也能恢复胰岛对葡萄糖刺激的胰岛素分泌的能力。（３）ＣＣＫ Ａ型受体阻断剂Ｌ３６４７１８（１０ｎｍｏｌ／Ｌ）能阻断ＣＣＫ－８的保护作用，表明这一作用可能是通过ＣＣＫ受体实现的。（４）ＩＬ－１β抑制胰岛素分泌的同时，能升高胰岛组织内ｃＧＭＰ水平，而ＣＣＫ－８能阻止ＩＬ－１引起的ｃＧＭＰ水平的升高。

The purpose of the present study was to investigate the effects of cholecystokinin-octapeptide(CCK-8)on interleukin-1β(IL-1β)inhibited insulin secretion in cultured newbornislets and its mechanism. The results were as follows:(1) IL-1β(5、10、20U/ml)signiflcantlyinhibited glucose-stimulated insulin secretion in a dose-dependent manner,with the inhibitoryrate being 53.4%、60.5% and 70.7%, respectively.(2)Administration of CCK- 8(10￣(-10), 10￣(-9),10￣(-8) and 10￣(- 7)mol/ L) either before or after IL-1βcould abolish the inhibitory effect of IL-1β.(3)CCK A-type receptor antagonist L364718(10nmol/L) could block this protective effect ofCCK-8.(4)IL-1β(10U/ml) increased the level of cGMP in islets and CCK-8(10￣(-9)mol/L)could prevent IL-1β from increasing the level of cGMP. These results indicate that CCK-8 canprotect the function of islet cells against the injurious effect of IL-1β. This action of CCK-8 isprobably mediated by CCK receptor and may be related to the reduction of nitric oxide produc-tion.