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胆囊收缩素诱导的急性胰腺炎发病机制中神经肽的作用。

Galanin mediates the pathogenesis of cerulein-induced acute pancreatitis in the mouse.

机构信息

Department of General and Digestive Surgery, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.

出版信息

Pancreas. 2010 Mar;39(2):182-7. doi: 10.1097/MPA.0b013e3181bdc152.

DOI:10.1097/MPA.0b013e3181bdc152
PMID:19959967
Abstract

OBJECTIVES

Acute pancreatitis (AP) is characterized by pancreatic microcirculatory and secretory disturbances. As galanin can modulate pancreatic vascular perfusion, we sought to determine if galanin plays a role in AP.

METHODS

Acute pancreatitis was induced in wild-type and galanin gene knockout mice by intraperitoneal injections of cerulein. The severity of AP was evaluated (plasma amylase and lipase, myeloperoxidase activity, and acinar cell necrosis) with and without treatment with galanin or the antagonist galantide. Galanin receptor messenger RNA expression in mouse pancreas was measured by reverse transcription-polymerase chain reaction and Western blot analysis.

RESULTS

Galantide ameliorated AP, reducing all indices by 25% to 40%, whereas galanin was without effect. In galanin knockout mice, all indices of AP were reduced 25% to 50% compared with wild-type littermates. Galanin administration to the knockout mice exacerbated AP such that it was comparable with the AP induced in the wild-type mice. Conversely, administration of galantide to the galanin knockout mice did not affect the AP, whereas AP was ameliorated in the wild-type mice. The 3 galanin receptor subtypes are expressed in mouse pancreas, with receptor subtype 3 expression predominating.

CONCLUSIONS

These data implicate a role for galanin in AP and suggest a potential clinical application for galanin antagonists in treatment.

摘要

目的

急性胰腺炎(AP)的特征是胰腺微循环和分泌功能紊乱。由于甘丙肽可以调节胰腺的血管灌注,我们试图确定甘丙肽是否在 AP 中起作用。

方法

通过腹腔注射 cerulein 在野生型和甘丙肽基因敲除小鼠中诱导急性胰腺炎。用甘丙肽或拮抗剂 galantide 治疗和不治疗时,评估 AP 的严重程度(血浆淀粉酶和脂肪酶、髓过氧化物酶活性和腺泡细胞坏死)。通过逆转录-聚合酶链反应和 Western blot 分析测量小鼠胰腺中的甘丙肽受体信使 RNA 表达。

结果

Galantide 改善了 AP,将所有指标降低了 25%至 40%,而甘丙肽则没有效果。与野生型同窝仔相比,甘丙肽敲除小鼠的所有 AP 指标均降低了 25%至 50%。甘丙肽给药至敲除小鼠可加重 AP,使其与野生型小鼠诱导的 AP 相当。相反,甘丙肽拮抗剂给药至甘丙肽敲除小鼠不会影响 AP,而在野生型小鼠中则改善了 AP。3 种甘丙肽受体亚型在小鼠胰腺中表达,以受体亚型 3 表达为主。

结论

这些数据表明甘丙肽在 AP 中起作用,并提示甘丙肽拮抗剂在治疗中的潜在临床应用。

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