抗凝血酶 III 可预防雨蛙肽诱导的大鼠急性胰腺炎。

Antithrombin III prevents cerulein-induced acute pancreatitis in rats.

机构信息

Departments of Anesthesiology and Intensive Care Medicine, Oita University, Yufu City, Japan.

出版信息

Pancreas. 2009 Oct;38(7):746-51. doi: 10.1097/MPA.0b013e3181aba9fa.

DOI:10.1097/MPA.0b013e3181aba9fa

PMID:19546838

Abstract

OBJECTIVES

Systemic inflammatory mediators, including the protein high-mobility group box 1 (HMGB1), play an important role in the development of acute pancreatitis. Anticoagulants, such as antithrombin III (AT III), inhibit inflammation resulting from various causes, but their mechanism of action is not well understood. Because acute pancreatitis is a severe inflammatory disease, we hypothesized that AT III would inhibit inflammation and prevent cerulein-induced acute pancreatitis.

METHODS

Experimental animals received or were saline injected with a bolus of 250 IU/kg of AT III followed by intraperitoneal injections of 50 mg/kg of cerulein. Levels of cytokines (interleukin 6 and tumor necrosis factor alpha), nitric oxide (NO), and HMGB1 were measured in serum and pancreatic tissue at regular intervals for 12 hours after the cerulein injection.

RESULTS

Pancreas histopathology and wet-dry ratio significantly improved in the AT III-injected (250 IU/kg) animals compared with the saline-injected rats. Serum and pancreas HMGB1 levels decreased over time in AT III-treated animals. Antithrombin III also decreased cytokine, NO, and HMGB1 levels during cerulein-induced inflammation. As a result, AT III ameliorated the pathologic pancreas in the rat model of cerulein-induced acute pancreatitis.

CONCLUSIONS

Antithrombin III treatment inhibited the secretion of cytokines, NO, and HMGB1 and prevented cerulein-induced acute pancreatitis in the rat model.

摘要

目的

全身性炎症介质，包括高迁移率族蛋白 B1（HMGB1），在急性胰腺炎的发展中起重要作用。抗凝剂，如抗凝血酶 III（AT III），抑制各种原因引起的炎症，但它们的作用机制尚不清楚。由于急性胰腺炎是一种严重的炎症性疾病，我们假设 AT III 将抑制炎症并预防雨蛙肽诱导的急性胰腺炎。

方法

实验动物接受或注射 250IU/kg 的 AT III 后，再给予 50mg/kg 的雨蛙肽腹腔注射。在雨蛙肽注射后 12 小时内，每隔一段时间测量血清和胰腺组织中的细胞因子（白细胞介素 6 和肿瘤坏死因子-α）、一氧化氮（NO）和 HMGB1 的水平。

结果

与生理盐水注射大鼠相比，AT III 注射（250IU/kg）动物的胰腺组织病理学和湿干比显著改善。AT III 治疗组的血清和胰腺 HMGB1 水平随时间推移而降低。抗凝血酶 III 还降低了雨蛙肽诱导的炎症期间细胞因子、NO 和 HMGB1 的水平。因此，AT III 改善了雨蛙肽诱导的急性胰腺炎大鼠模型中的病理性胰腺。