Araki H, Nishihara T, Matsuda M, Fukuhara A, Kihara S, Funahashi T, Kataoka T R, Kamada Y, Kiyohara T, Tamura S, Hayashi N, Shimomura I
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, K1, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Gut. 2008 Oct;57(10):1431-40. doi: 10.1136/gut.2007.135665. Epub 2008 Jun 25.
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.
To determine the effects of adiponectin on AP.
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 microg/kg) after 2 week feeding of normal chow or a high-fat diet (HFD) in wild-type (WT) and APN-KO mice. We evaluated the severity of AP biochemically and morphologically.
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 alpha in the pancreas. Adenovirus-mediated over-expression of adiponectin attenuated the severity of HFD/caerulein-induced AP in APN-KO mice.
Adiponectin plays a protective role in caerulein-induced AP in HFD-fed mice.
肥胖是急性胰腺炎(AP)的一个危险因素,但其分子机制仍不清楚。脂联素是一种脂肪组织衍生的分泌因子,除了具有多种生物学功能外,还具有抗炎特性,肥胖受试者的血浆脂联素浓度会降低。然而,脂联素在急性胰腺炎中的作用尚未得到研究。
确定脂联素对急性胰腺炎的影响。
我们通过使用脂联素基因敲除(APN-KO)小鼠和腺病毒介导的脂联素过表达,研究了脂联素对实验性急性胰腺炎的影响。在野生型(WT)和APN-KO小鼠正常饮食或高脂饮食(HFD)喂养2周后,通过每小时腹腔注射低剂量雨蛙素(10微克/千克),连续注射10次来诱导急性胰腺炎。我们从生化和形态学方面评估了急性胰腺炎的严重程度。
在正常饮食喂养下,低剂量雨蛙素处理在WT或APN-KO小鼠中均未诱导胰腺损伤。喂食高脂饮食然后用雨蛙素处理的APN-KO小鼠,而非WT小鼠,出现了胰腺损伤和炎症,伴有巨噬细胞/中性粒细胞浸润增加以及胰腺中肿瘤坏死因子α等促炎介质的上调。腺病毒介导的脂联素过表达减轻了APN-KO小鼠中高脂饮食/雨蛙素诱导的急性胰腺炎的严重程度。
脂联素在高脂饮食喂养的小鼠中,对雨蛙素诱导的急性胰腺炎起保护作用。