Adiponectin plays a protective role in caerulein-induced acute pancreatitis in mice fed a high-fat diet
Adiponectin plays a protective role in caerulein-induced acute pancreatitis in mice fed a high-fat diet
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DOI：
10.1136/gut.2007.135665
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发表时间：
2008-10-01
期刊：
影响因子：
24.5
通讯作者：
Shimomura, I.
中科院分区：
文献类型：
--
作者：
Araki, H.;Nishihara, T.;Shimomura, I.
背景：肥胖是急性胰腺炎(AP)的危险因素，但其分子机制尚不清楚。脂联素是一种脂肪组织源性分泌因子，除了具有多种生物学功能外，还具有抗炎作用，肥胖者血浆中脂联素浓度降低。然而，脂联素在AP中的作用尚未被研究。目的：探讨脂联素对急性胰腺炎的影响。方法：采用脂联素基因敲除小鼠(APN-KO)和腺病毒介导的脂联素过表达模型，观察脂联素对实验性AP的影响。野生型(WT)和APN-KO小鼠在喂饲正常饲料或高脂饲料(HFD)2周后，每小时腹腔注射10 mg/kg小剂量雨蛙素(10 mg/kg)诱发AP。我们对AP的严重程度进行了生化和形态学评估。结果：在正常喂养条件下，小剂量雨蛙素对WT和APN-KO小鼠均无胰腺损伤作用。APN-KO小鼠，而不是WT小鼠，喂食HFD，然后用雨蛙素治疗，出现胰腺损伤和炎症，伴随着巨噬细胞/中性粒细胞浸润增加，胰腺中促炎症介质，如肿瘤坏死因子a上调。腺病毒介导的脂联素过表达减轻HFD/雨蛙素诱导的APN-KO小鼠AP的严重程度。结论：脂联素对雨蛙素诱导的高脂饮食小鼠急性胰腺炎有保护作用。
Background: Obesity is a risk factor for acute pancreatitis (AP), but the molecular mechanism remains unclear. Adiponectin, an adipose tissue-derived secretory factor, has anti-inflammatory properties in addition to various biological functions, and its plasma concentrations are reduced in obese subjects. However, the role of adiponectin in AP has not been investigated. Aim: To determine the effects of adiponectin on AP. Methods: We investigated the effects of adiponectin on experimental AP by using adiponectin-knockout (APN-KO) mice and adenovirus-mediated adiponectin over-expression. AP was induced by 10 hourly intraperitoneal injections of low-dose caerulein (10 mg/kg) after 2 week feeding of normal chow or a high-fat diet (HFD) in wildtype (WT) and APN-KO mice. We evaluated the severity of AP biochemically and morphologically. Results: Low-dose caerulein treatment did not induce pancreatic damage in either WT or APN-KO mice under normal chow feeding. APN-KO mice, but not WT mice, fed a HFD and then treated with caerulein developed pancreatic damage and inflammation, accompanied by increased macrophage/neutrophil infiltration and upregulation of pro-inflammatory mediators such as tumour necrosis factor a in the pancreas. Adenovirus-mediated over-expression of adiponectin attenuated the severity of HFD/caerulein-induced AP in APN-KO mice. Conclusions: Adiponectin plays a protective role in caerulein-induced AP in HFD-fed mice.