Chronic Pancreatitis in Mice by Treatment with Choline-Deficient Ethionine-Supplemented Diet
Chronic Pancreatitis in Mice by Treatment with Choline-Deficient Ethionine-Supplemented Diet
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DOI：
10.1538/expanim.59.421
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发表时间：
2010-07-01
影响因子：
2.4
通讯作者：
Yamamura, Ken-ichi
中科院分区：
文献类型：
--
作者：
Ida, Satoshi;Ohmuraya, Masaki;Yamamura, Ken-ichi
虽然慢性胰腺炎是胰腺导管腺癌（PDA）的危险因素，但慢性胰腺炎与PDA之间的关系仍不清楚。了解慢性胰腺炎的作用的一个关键障碍是缺乏动物模型。为了开发一种这样的模型，用胆碱缺乏的乙硫氨酸补充（CDE）饮食长期喂养小鼠。组织学评价显示，CDE饮食治疗24周后观察到慢性胰腺炎，其特征为腺泡萎缩、纤维化和发育良好的管状复合体（TC）。此外，表皮生长因子受体（EGFR）及其配体、丝氨酸蛋白酶抑制剂Kazal 3型（Spink 3）和转化生长因子α（TGF α）的表达以及K-Ras的活化（GTP-Ras形成）（这些在人PDA中经常观察到）确实与TC形成平行观察到。治疗54周后未发现肿瘤性病变，表明PDA的发生需要继续CDE饮食或其他损伤。
Although chronic pancreatitis is a risk factor for pancreatic ductal adenocarcinoma (PDA), the relationship between chronic pancreatitis and PDA remains obscure. A critical obstacle to understanding the role of chronic pancreatitis is the lack of animal models. To develop one such model, mice were fed long-term with a choline deficient ethionine-supplemented (CDE) diet. Histological evaluation revealed that chronic pancreatitis, characterized by acinar atrophy, fibrosis and well-developed tubular complexes (TCs), was observed after 24 weeks of CDE diet treatment. Furthermore, expression of epidermal growth factor receptor (EGFR) and its ligands; serine protease inhibitor Kazal type 3 (Spink3) and transforming growth factor alpha (TGF alpha) and activation of K-Ras (GTP-Ras formation), which are frequently observed in human PDA, were indeed observed in parallel with TCs formation. Neoplastic lesions were not found after 54 weeks of treatment, suggesting that a continuation of CDE diet or another insult is required for the development of PDA.