Overactivity of the intestinal endocannabinoid system in celiac disease and in methotrexate-treated rats
Overactivity of the intestinal endocannabinoid system in celiac disease and in methotrexate-treated rats
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DOI：
10.1007/s00109-007-0192-3
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发表时间：
2007-05-01
影响因子：
4.7
通讯作者：
Di Marzo, Vincenzo
中科院分区：
文献类型：
--
作者：
D'Argenio, Giuseppe;Petrosino, Stefania;Di Marzo, Vincenzo
内源性大麻素系统在人类炎症性肠病和结肠炎实验模型中均上调。在这项研究中，我们调查了这种上调是否也是乳糜泻引起的萎缩的标志物。大麻素CB 1受体，内源性大麻素，大麻素，2-花生四烯酸-甘油（2-AG），和抗炎介质棕榈酰乙醇胺（PEA）的水平进行了分析，活检样品从腹腔患者的十二指肠粘膜在第一次诊断评估的抗肌内膜抗体的测定和组织学检查。在萎缩的活动期和缓解后分析样品，并与来自非乳糜泻患者的对照样品进行比较。花生四烯酸和PEA的水平显著升高（约为100 mg/kg）。2-和1.8倍），CB 1受体也是如此。无麸质饮食缓解后，花生四烯酸水平恢复正常。我们还分析了内源性大麻素和PEA水平在空肠的大鼠治疗后2，3，7天与甲氨蝶呤，这会导致炎症特征（通过组织病理学分析和髓过氧化物酶活性评估）相似的腹腔患者。在肌肉/浆膜和粘膜层中，花生四烯酸、2-AG和PEA的水平在治疗后3天达到峰值，并在治疗后7天缓解时恢复到基础水平。因此，在乳糜泻患者和甲氨蝶呤治疗的大鼠中，肠内源性大麻素水平在萎缩时达到峰值，并在缓解时消退。后者可用作研究内源性大麻素系统在乳糜泻中的作用的模型。
The endocannabinoid system is upregulated in both human inflammatory bowel diseases and experimental models of colitis. In this study, we investigated whether this upregulation is a marker also of celiac disease-induced atrophy. The levels of the cannabinoid CB1 receptor, of the endocannabinoids, anandamide, and 2-arachidonoyl-glycerol (2-AG), and of the anti-inflammatory mediator palmitoylethanolamide (PEA) were analyzed in bioptic samples from the duodenal mucosa of celiac patients at first diagnosis assessed by the determination of antiendomysial antibodies and histological examination. Samples were analyzed during the active phase of atrophy and after remission and compared to control samples from non-celiac patients. The levels of anandamide and PEA were significantly elevated (approx. 2- and 1.8-fold, respectively) in active celiac patients and so were those of CB1 receptors. Anandamide levels returned to normal after remission with a gluten-free diet. We also analyzed endocannabinoid and PEA levels in the jejunum of rats 2, 3, and 7 days after treatment with methotrexate, which causes inflammatory features (assessed by histopathological analyses and myeloperoxidase activity) similar to those of celiac patients. In both muscle/serosa and mucosa layers, the levels of anandamide, 2-AG, and PEA peaked 3 days after treatment and returned to basal levels at remission, 7 days after treatment. Thus, intestinal endocannabinoid levels peak with atrophy and regress with remission in both celiac patients and methotrexate-treated rats. The latter might be used as a model to study the role of the endocannabinoid system in celiac disease.