Department of General and Digestive Surgery, Flinders Medical Centre and Flinders University, Adelaide, South Australia, Australia.
Peptides. 2010 Feb;31(2):315-21. doi: 10.1016/j.peptides.2009.11.014. Epub 2009 Nov 26.
Both galanin and substance P have been separately implicated in the pathogenesis of acute pancreatitis. We compared the efficacy of the combination of the galanin antagonist galantide and the neurokinin-1 receptor antagonist L703,606 with that of either alone in the treatment of acute pancreatitis. Acute pancreatitis was induced in mice with 7-hourly caerulein injections. Galantide was co-administered with each caerulein injection commencing with the first injection (prophylactic) or 2h after the first injection (therapeutic). L703,606 was administered either 30 min before (prophylactic), or 2h after the first caerulein injection (therapeutic). Combination of the two agents was also administered. Control groups received galantide, L703,606, or saline, without caerulein. Pancreata were harvested for histological examination and estimation of myeloperoxidase activity. Plasma amylase activity was measured. Prophylactic and therapeutic administration of galantide reduced the hyperamylasemia by 37% and 30% respectively whereas only prophylactic L703,606 reduced hyperamylasemia (by 34%). Prophylactic administration of the combined antagonists reduced the hyperamylasemia by 44%. In contrast, therapeutic administration of the combination significantly increased plasma amylase levels by 27%. The plasma amylase activity in the control groups was similar to basal levels. Prophylactic and therapeutic administration of either antagonist or the combination significantly reduced myeloperoxidase activity. Galantide and L703,606 individually, and in combination, significantly reduced the acute pancreatitis-induced necrosis score. The administration of the combined antagonists does not offer any further benefit as compared to galantide alone. An interaction between neurokinin-1 and galanin receptors may occur to modulate amylase secretion.
甘丙肽和 P 物质都分别被牵连到急性胰腺炎的发病机制中。我们比较了甘丙肽拮抗剂甘丙肽和神经激肽-1 受体拮抗剂 L703,606 联合使用与单独使用治疗急性胰腺炎的疗效。通过 7 小时的蛙皮素注射诱导小鼠发生急性胰腺炎。甘丙肽与每次蛙皮素注射同时给予（预防），或在第一次注射后 2 小时给予（治疗）。L703,606 在第一次蛙皮素注射前 30 分钟给予（预防），或在第一次注射后 2 小时给予（治疗）。两种药物的联合也进行了给药。对照组接受甘丙肽、L703,606 或生理盐水，而不接受蛙皮素注射。收获胰腺进行组织学检查和髓过氧化物酶活性测定。测量血浆淀粉酶活性。预防性和治疗性给予甘丙肽分别使高淀粉酶血症降低 37%和 30%，而只有预防性 L703,606 降低高淀粉酶血症（降低 34%）。联合拮抗剂的预防性给药使高淀粉酶血症降低 44%。相比之下，联合给药的治疗性给药使血浆淀粉酶水平升高 27%。对照组的血浆淀粉酶活性与基础水平相似。预防性和治疗性给予任一拮抗剂或联合均可显著降低髓过氧化物酶活性。甘丙肽和 L703,606 单独或联合使用均显著降低急性胰腺炎诱导的坏死评分。与单独使用甘丙肽相比，联合使用拮抗剂并没有提供任何额外的益处。神经激肽-1 和甘丙肽受体之间可能发生相互作用，以调节淀粉酶分泌。
