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甘丙肽受体拮抗剂 m35 而非 m40 或 c7 可改善小鼠的雨蛙肽诱导的急性胰腺炎。

Galanin receptor antagonist m35 but not m40 or c7 ameliorates cerulein-induced acute pancreatitis in mice.

机构信息

Departments of General and Digestive Surgery, Flinders Medical Centre, Flinders University, Adelaide, S.A., Australia.

出版信息

Pancreatology. 2010;10(6):682-8. doi: 10.1159/000314603. Epub 2011 Jan 18.

DOI:10.1159/000314603
PMID:21242707
Abstract

BACKGROUND/AIMS: We compared the galanin antagonists C7, M35, M40 and galantide, for their ability to ameliorate acute pancreatitis (AP).

METHODS

Galanin antagonists were co-administered with 7 hourly cerulein injections used to induce AP. Plasma amylase and lipase activities were measured as indices of AP, and pancreata were harvested at 12 h for histological examination and estimation of myeloperoxidase (MPO) activity.

RESULTS

Treatment with galantide, M35 and C7 ameliorated the AP-induced plasma hyperenzymemia by 40-75%. Administration of M40 did not significantly alter plasma hyperenzymemia. Galantide, M35 and M40 significantly reduced the pancreatic MPO activity by 65-80%, whereas C7 increased MPO activity. Galantide and M35 but not C7 or M40 treatment significantly reduced the AP-induced necrosis score by 30-50% compared to the AP alone group. C7 alone increased plasma lipase activity and the pancreatic necrosis score compared with saline treatment alone, whereas the other antagonists were without effect.

CONCLUSION

Galantide and M35 ameliorated the severity of AP, but M40 and C7 had mixed effects. Complex galanin pathways may be involved in cerulein-induced AP. M35 and galantide are potential therapeutic peptides for the treatment of AP and further evaluation should be considered. and IAP.

摘要

背景/目的:我们比较了甘丙肽拮抗剂 C7、M35、M40 和甘丙肽,以评估它们改善急性胰腺炎(AP)的能力。

方法

甘丙肽拮抗剂与 7 小时一次的 cerulein 注射同时给药,用于诱导 AP。血浆淀粉酶和脂肪酶活性作为 AP 的指标进行测量,胰腺在 12 小时收获进行组织学检查和髓过氧化物酶(MPO)活性估计。

结果

甘丙肽、M35 和 C7 治疗可使 AP 诱导的血浆高酶血症改善 40-75%。M40 给药不能显著改变血浆高酶血症。甘丙肽、M35 和 M40 可使胰腺 MPO 活性降低 65-80%,而 C7 增加 MPO 活性。与仅 AP 组相比,甘丙肽和 M35 治疗可使 AP 诱导的坏死评分降低 30-50%,但 C7 或 M40 治疗则没有。C7 单独治疗与生理盐水单独治疗相比,可增加血浆脂肪酶活性和胰腺坏死评分,而其他拮抗剂则没有影响。

结论

甘丙肽和 M35 可改善 AP 的严重程度,但 M40 和 C7 则具有混合作用。复杂的甘丙肽途径可能参与 cerulein 诱导的 AP。M35 和甘丙肽是治疗 AP 的潜在治疗性肽,应进一步考虑进行评估。

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