Bozkurt Ayhan, Cakir Bariş, Ercan Feriha, Yeğen Berrak C
Department of Physiology, School of Medicine, Marmara University, Haydarpaşa, Istanbul, 34668, Turkey.
Regul Pept. 2003 Nov 15;116(1-3):109-18. doi: 10.1016/s0167-0115(03)00194-0.
Leptin and cholecystokinin (CCK) have a synergistic interaction in the suppression of food intake, and afford similar gastroprotective activity. The present study was designed to investigate the putative protective effects of CCK and leptin on acute colonic inflammation. Leptin or CCK-8s was injected to rats intraperitoneally immediately before and 6 h after the induction of colitis with acetic acid. CCK-A receptor antagonist (L-364,718) or CCK-B receptor antagonist (L-365,260) was injected intraperitoneally 15 min before leptin or CCK treatments. In a group of rats, vagal afferent fibers were denervated by topical application of capsaicin on the cervical vagi. Rats were decapitated at 24 h, and the distal 8 cm of the colon were removed for macroscopic scoring, determination of tissue wet weight index (WWI), histologic assessment and tissue myeloperoxidase (MPO) activity. All inflammation parameters were increased by acetic acid-induced colitis compared to control group. Leptin or CCK-8s treatment reduced these parameters in a similar manner, while co-administration of leptin and CCK was found to be more effective in reducing the macroscopic score and WWI. CCK-8s-induced reduction in the score and WWI was prevented by CCK-A, but not by CCK-B receptor antagonist, whereas neither antagonist altered the inhibitory effect of leptin on colitis-induced injury. On the other hand, perivagal capsaicin prevented the protective effects of both CCK-8s and leptin on colitis. Our results indicate that leptin and CCK have anti-inflammatory effects on acetic acid-induced colitis in rats, which appear to be mediated by capsaicin-sensitive vagal afferent fibers involving the reduction in colonic neutrophil infiltration.
瘦素和胆囊收缩素（CCK）在抑制食物摄入方面具有协同作用，并具有相似的胃保护活性。本研究旨在探讨CCK和瘦素对急性结肠炎症的假定保护作用。在用乙酸诱导结肠炎之前和之后6小时，立即给大鼠腹腔注射瘦素或CCK-8s。在给予瘦素或CCK治疗前15分钟，腹腔注射CCK-A受体拮抗剂（L-364,718）或CCK-B受体拮抗剂（L-365,260）。在一组大鼠中，通过在颈迷走神经上局部应用辣椒素来切断迷走神经传入纤维。24小时后将大鼠断头，取出结肠远端8厘米进行宏观评分、测定组织湿重指数（WWI）、组织学评估和组织髓过氧化物酶（MPO）活性。与对照组相比，乙酸诱导的结肠炎增加了所有炎症参数。瘦素或CCK-8s治疗以类似方式降低了这些参数，而发现联合给予瘦素和CCK在降低宏观评分和WWI方面更有效。CCK-A受体拮抗剂可阻止CCK-8s引起的评分和WWI降低，但CCK-B受体拮抗剂则不能，而两种拮抗剂均未改变瘦素对结肠炎诱导损伤的抑制作用。另一方面，迷走神经周围应用辣椒素可阻止CCK-8s和瘦素对结肠炎的保护作用。我们的结果表明，瘦素和CCK对大鼠乙酸诱导的结肠炎具有抗炎作用，这似乎是由辣椒素敏感的迷走神经传入纤维介导的，涉及结肠中性粒细胞浸润的减少。
