Gut barrier dysfunction in the Apc(Min/+) mouse model of colon cancer cachexia.
Gut barrier dysfunction in the Apc(Min/+) mouse model of colon cancer cachexia.
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DOI：
10.1016/j.bbadis.2011.08.010
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Carson JA
中科院分区：
文献类型：
--
作者：
Puppa MJ;White JP;Sato S;Cairns M;Baynes JW;Carson JA
ApcMin/+小鼠是结直肠癌和恶病质的动物模型，APC肿瘤抑制基因存在异源突变，使小鼠容易发生肠道和结肠肿瘤。这种小鼠在~4周龄时出现肠息肉，并在~14周龄至~20周龄期间逐渐减重。这种恶病质模型的优势来自于模仿人类癌症的几个特征，包括肿瘤负担逐渐增加、慢性炎症和贫血。关于肠道屏障功能障碍和内毒素血症在癌症恶病质发生中的作用，人们知之甚少。我们试图确定肠道通透性和由此产生的内毒素血症如何随着恶病质的进展而变化。通过对FITC-葡聚糖(MWav=4,000 kDa；FD4)的通透性来评估肠屏障的完整性。血糖、甘油三酯测定采用酶法，IL-6测定采用ELISA法，内毒素测定采用变形细胞法。用直肠探头测量体温。恶病质的发展伴随着肠屏障功能障碍(对FD4的通透性)、肠系膜淋巴结肥大和血浆内毒素浓度的增加。血糖和糖耐量、血浆IL-6、甘油三酯和体温的变化是内毒素血症的特征。我们提出肠屏障功能障碍(GBD)和随后的内毒素血症在ApcMin/+小鼠炎症和恶病质进展中的作用。
The ApcMin/+ mouse, an animal model of colorectal cancer and cachexia, has a heterologous mutation in the Apc tumor suppressor gene, predisposing the mouse to intestinal and colon tumor development. This mouse develops intestinal polyps by ~4 weeks of age, and loses body weight gradually between ~14 and ~20 weeks of age. The strengths of this cachexia model derive from several features that mimic human cancer, including a gradual increase in tumor burden, chronic inflammation, and anemia. Little is known about the role of gut barrier dysfunction and endotoxemia in the development of cancer cachexia. We sought to determine how gut permeability and resultant endotoxemia change with the progression of cachexia. Intestinal gut barrier integrity was assessed by permeability to FITC-dextran (MWav = 4,000 kDa; FD4). Plasma glucose and triglycerides were measured by enzymatic assays, IL-6 by ELISA, and endotoxin by the limulus amoebocyte assay. Body temperature was measured using a rectal probe. Progression of cachexia was accompanied by development of gut barrier dysfunction (permeability to FD4), hypertrophy of mesenteric lymph nodes, and an increase in plasma endotoxin concentration. Changes in blood glucose and glucose tolerance, plasma IL-6, triglycerides, and body temperature were characteristic of endotoxemia. We propose a role for gut barrier dysfunction (GBD) and subsequent endotoxemia in the development of inflammation and progression of cachexia in the ApcMin/+ mouse.
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影响因子：
3.1
作者：
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通讯作者：
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