Improta Giovanna, Carpino Francesco, Petrozza Vincenzo, Guglietta Antonio, Tabacco Alessandra, Broccardo Maria
Department of Human Physiology and Pharmacology, University La Sapienza, Ple A. Moro 5-00185, Rome, Italy.
Peptides. 2003 Jun;24(6):903-11. doi: 10.1016/s0196-9781(03)00161-x.
Peripheral tachykinins (TKs) are believed to play a role in the pathogenesis of inflammatory bowel diseases (IBD). In this study we investigated changes induced by central administration of two natural TK receptor agonists, NK(1) (PG-SPI) and NK(3) (PG-KII), on trinitrobenzene sulphonic acid (TNBS)- and dextran sodium sulphate (DSS)-induced experimental colitis in rats. Colitis was induced by instilling a single intracolonic dose of TNBS 50 mgkg(-1) (0.5 ml in 50% ethanol) or by oral administration of 5% DSS for 7 days. Each group of rats was intracerebroventricularly injected daily with PG-SPI and PG-KII (0.5, 5, and 50 microgkg(-1)). On day 3, TNBS-treated animals were killed and the severity of gut inflammation was evaluated by measuring myeloperoxidase (MPO) activity, interleukin-1beta (IL-1beta) production and by scoring macroscopic and histologic colonic damage. DSS-treated animals were checked daily for the length of survival and for stool consistency and faecal blood. In the TNBS group, PG-SPI and PG-KII increased scores for the severity of colonic damage, stimulated the production of IL-1beta and increased granulocyte infiltration into the colon (MPO activity). In the DSS group, PG-SPI and PG-KII decreased the percentage of surviving animals, and increased the number of rats that developed loose stools and blood in the faeces and the MPO activity. These results indicate that centrally injected NK(1) and NK(3) tachykinin receptor agonists play a proinflammatory role in experimentally-induced colitis in rats.
外周速激肽（TKs）被认为在炎症性肠病（IBD）的发病机制中起作用。在本研究中，我们调查了中枢给予两种天然TK受体激动剂NK(1)（PG-SPI）和NK(3)（PG-KII）对三硝基苯磺酸（TNBS）和葡聚糖硫酸钠（DSS）诱导的大鼠实验性结肠炎的影响。通过结肠内单次注入50 mgkg(-1)的TNBS（在50%乙醇中0.5 ml）或口服5% DSS 7天来诱导结肠炎。每组大鼠每天经脑室内注射PG-SPI和PG-KII（0.5、5和50 microgkg(-1)）。在第3天，处死TNBS处理的动物，通过测量髓过氧化物酶（MPO）活性、白细胞介素-1β（IL-1β）产生以及对结肠宏观和组织学损伤进行评分来评估肠道炎症的严重程度。每天检查DSS处理的动物的存活时间、粪便稠度和粪便潜血情况。在TNBS组中，PG-SPI和PG-KII增加了结肠损伤严重程度的评分，刺激了IL-1β的产生，并增加了粒细胞向结肠的浸润（MPO活性）。在DSS组中，PG-SPI和PG-KII降低了存活动物的百分比，并增加了出现稀便和粪便带血的大鼠数量以及MPO活性。这些结果表明，经中枢注射的NK(1)和NK(3)速激肽受体激动剂在大鼠实验性结肠炎中起促炎作用。
