D'Argenio Giuseppe, Petrosino Stefania, Gianfrani Carmen, Valenti Marta, Scaglione Giuseppe, Grandone Ilenia, Nigam Santosh, Sorrentini Italo, Mazzarella Giuseppe, Di Marzo Vincenzo
Dipartimento di Gastroenterologia, Università di Napoli Federico II, Naples, Italy.
J Mol Med (Berl). 2007 May;85(5):523-30. doi: 10.1007/s00109-007-0192-3. Epub 2007 Mar 30.
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 CB(1) 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 CB(1) 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.
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。在本研究中，我们调查了这种上调是否也是乳糜泻诱导萎缩的一个标志物。通过抗肌内膜抗体测定和组织学检查，对初诊乳糜泻患者十二指肠黏膜活检样本中的大麻素CB(1)受体、内源性大麻素、花生四烯酸乙醇胺（AEA）和2-花生四烯酸甘油酯（2-AG）以及抗炎介质棕榈酰乙醇胺（PEA）水平进行了分析。在萎缩的活动期和缓解期对样本进行分析，并与非乳糜泻患者的对照样本进行比较。活动期乳糜泻患者的AEA和PEA水平显著升高（分别约为2倍和1.8倍），CB(1)受体水平也是如此。采用无麸质饮食缓解后，AEA水平恢复正常。我们还分析了用甲氨蝶呤治疗2、3和7天后大鼠空肠中的内源性大麻素和PEA水平，甲氨蝶呤会引发与乳糜泻患者相似的炎症特征（通过组织病理学分析和髓过氧化物酶活性评估）。在肌层/浆膜层和黏膜层中，AEA、2-AG和PEA水平在治疗后3天达到峰值，并在治疗7天后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，肠道内源性大麻素水平在萎缩时达到峰值，并在缓解时回归正常。后者可作为研究内源性大麻素系统在乳糜泻中作用的模型。
