Department of General and Digestive Surgery, Flinders Medical Centre and Flinders University, Bedford Park, Adelaide 5042, South Australia, Australia.
Peptides. 2010 Jun;31(6):1076-82. doi: 10.1016/j.peptides.2010.02.027. Epub 2010 Mar 7.
We have previously shown that galantide ameliorates mild acute pancreatitis (AP), and the salivary tripeptide analogue, feG, ameliorates severe AP in mice. In this study, we compared the efficacy of combining galantide and feG with that of the individual agents in treating mild AP induced in mice with 7-hourly caerulein injections. Galantide was co-administered with each caerulein injection commencing with the first injection. feG was co-administered with the first injection of caerulein as a single intraperitoneal injection. Combination of the agents was also administered. Control animals received galantide, feG, or saline alone. Pancreata were harvested for histological examination and estimation of myeloperoxidase (MPO) activity. Plasma enzyme activities were measured. Galantide significantly reduced AP-induced hyperenzymemia by 41-49%. The combination of galantide and feG significantly reduced AP-induced hyperenzymemia by 39-40%, whereas feG alone was without effect. Plasma enzyme activity in the control groups was comparable with pre-treatment activity. Galantide, feG, and their combination significantly reduced MPO activity by 83, 44 and 74% respectively, and % abnormal acinar cells by 32, 29 and 36% respectively. This study demonstrates for the first time the beneficial effect of feG in mild caerulein-induced AP. Moreover the data indicate that the hyperenzymemia in mild caerulein-induced AP at 12h possibly reflect a larger secretory component as compared to enzyme release due to neutrophil-mediated acinar cell damage. The effects of the treatment with both peptides indicate a possible role for galantide in modulating neutrophil chemotaxis/activation and supports the hypothesis that galantide may influence neurogenic inflammation in AP.
我们之前已经表明，加兰肽可改善轻度急性胰腺炎（AP），唾液三肽类似物 feG 可改善小鼠的重症 AP。在这项研究中，我们比较了加兰肽和 feG 联合与单独使用这两种药物治疗用 7 小时间隔的蛙皮素注射诱导的小鼠轻度 AP 的疗效。加兰肽与第一次蛙皮素注射同时给药。feG 作为单次腹腔内注射与第一次蛙皮素注射同时给药。还给予联合用药。对照动物单独接受加兰肽、feG 或生理盐水。采集胰腺进行组织学检查和髓过氧化物酶（MPO）活性测定。测定血浆酶活性。加兰肽可使 AP 诱导的高酶血症降低 41-49%。加兰肽和 feG 的联合使用可使 AP 诱导的高酶血症降低 39-40%，而 feG 单独使用则没有效果。对照组的血浆酶活性与治疗前的活性相当。加兰肽、feG 和它们的组合分别使 MPO 活性降低 83%、44%和 74%，异常腺泡细胞的百分比分别降低 32%、29%和 36%。本研究首次证明了 feG 在轻度蛙皮素诱导的 AP 中的有益作用。此外，数据表明，12 小时轻度蛙皮素诱导的 AP 中的高酶血症可能反映了更大的分泌成分，而不是由于中性粒细胞介导的腺泡细胞损伤导致的酶释放。两种肽的治疗效果表明加兰肽可能在调节中性粒细胞趋化/激活中起作用，并支持加兰肽可能影响 AP 中神经源性炎症的假说。
