Adiponectin deficiency enhanced the severity of cerulein-induced chronic pancreatitis in mice
Adiponectin deficiency enhanced the severity of cerulein-induced chronic pancreatitis in mice
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DOI：
10.1007/s00535-010-0205-9
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发表时间：
2010-02
影响因子：
6.3
通讯作者：
Takuya Yamada;H. Araki;K. Watabe;Y. Kamada;S. Kiso;H. Ogiyama;Tamao Nishihara;S. Kihara;T. Funahashi;I. Shimomura;S. Tsutsui;N. Hayashi
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作者：
Takuya Yamada;H. Araki;K. Watabe;Y. Kamada;S. Kiso;H. Ogiyama;Tamao Nishihara;S. Kihara;T. Funahashi;I. Shimomura;S. Tsutsui;N. Hayashi
脂联素被认为是一种来源于脂肪细胞的抗炎和抗纤维化蛋白，肥胖患者血清脂联素水平低。最近的研究强调了肥胖和胰腺疾病之间的关系。然而，脂联素在慢性胰腺炎中的作用仍不确定。本研究的目的是确定脂联素在慢性胰腺炎中的作用。方法采用脂联素敲除（APN-KO）小鼠研究脂联素在实验性慢性胰腺炎中的作用。野生型（WT）和APN-KO小鼠每小时（6次）腹腔注射50µg/kg蓝蛋白，每周3次，连续4周。我们从生化和形态学上评估慢性胰腺炎的严重程度。结果APN-KO小鼠与WT小鼠相比，在宏观和组织学上均出现了严重的胰腺损伤。慢性胰腺炎的组织学评分，包括腺萎缩、假小管复合体、纤维化和总分，APN-KO小鼠明显高于WT小鼠。激活的胰腺星状细胞和f4 /80阳性胰腺巨噬细胞在APN-KO小鼠胰腺中积累，而在WT小鼠中没有。在APN-KO小鼠中发现了转化生长因子-β1、CD68和单核细胞趋化蛋白-1 mrna的过表达，而在WT小鼠中没有。胶原- 1 （α1）基因表达水平在APN-KO小鼠中有高于WT小鼠的趋势，但差异不显著。结论脂联素缺乏可提高小白鼠慢性胰腺炎的严重程度。低脂联素血症可加重慢性胰腺炎的严重程度。
BackgroundAdiponectin is recognized as an antiinflammatory and antifibrotic protein derived from adipocytes, and low serum adiponectin levels are present in obesity. Recent studies have highlighted the relationship between obesity and pancreatic diseases. However, the role of adiponectin in chronic pancreatitis remains uncertain. The aim of this study was to determine the effects of adiponectin in chronic pancreatitis.MethodsWe investigated the effects of adiponectin in experimental chronic pancreatitis by using adiponectin-knockout (APN-KO) mice. Chronic pancreatitis was induced by repeated hourly (6 times) intraperitoneal injections of 50 µg/kg cerulein three times per week for 4 weeks in wild-type (WT) and APN-KO mice. We evaluated the severity of chronic pancreatitis biochemically and morphologically.ResultsIn cerulein-treated mice, macroscopically and histologically, severe pancreatic damage was observed in APN-KO mice compared with findings in WT mice. The histological scores for chronic pancreatitis, including glandular atrophy, pseudotubular complex, fibrosis, and total scores, were significantly higher in APN-KO mice than in WT mice. Activated pancreatic stellate cells and F4/80-positive pancreatic macrophages accumulated in the pancreas of APN-KO mice but not in WT mice. Overexpression of the mRNAs of transforming growth factor-β1, CD68, and monocyte chemoattractant protein-1 was noted in APN-KO mice but not in WT mice. The gene expression level of collagen1 (α1) tended to be higher in APN-KO mice than in WT mice, albeit insignificantly.ConclusionsAdiponectin deficiency enhanced the severity of cerulein-induced chronic pancreatitis in mice. Hypoadiponectinemia could enhance the severity of chronic pancreatitis.