First Department of Medicine, Fondazione IRCCS Policlinico S. Matteo, Centro per lo Studio e la Cura delle Malattie Infiammatorie Croniche Intestinali, University of Pavia, Pavia, Italy.
Mucosal Immunol. 2011 Sep;4(5):574-83. doi: 10.1038/mi.2011.18. Epub 2011 Apr 6.
Activation of cannabinoid receptors (CBs) by endocannabinoids impacts on a number of gastrointestinal functions. Recent data indicate that CB1 agonists improve 2,4-dinitrobenzene sulfonic acid-induced colitis in mice, thus suggesting a role for the endocannabinoid agonist anandamide (AEA) in protecting the gut against inflammation. We here examined the gut endocannabinoid system in inflammatory bowel disease (IBD) patients, and investigated the ex vivo and in vitro effects of the non-hydrolysable AEA analog methanandamide (MAEA) on the mucosal proinflammatory response. The content of AEA, but not of 2-arachidonoyl-glycerol and N-palmitoylethanolamine, was significantly lower in inflamed than uninflamed IBD mucosa, and this was paralleled by lower activity of the AEA-synthesizing enzyme N-acyl-phosphatidylethanolamine-specific phospholipase D and higher activity of the AEA-degrading enzyme fatty acid amide hydrolase. MAEA significantly downregulated interferon-γ and tumor necrosis factor-α secretion by both organ culture biopsies and lamina propria mononuclear cells. Although these results are promising, further studies are needed to determine the role of cannabinoid pathways in gut inflammation.
内源性大麻素受体（CBs）的激活受内源性大麻素的影响，对许多胃肠道功能都有影响。最近的数据表明，CB1 激动剂可改善二硝基苯磺酸诱导的小鼠结肠炎，这表明内源性大麻素激动剂大麻素（AEA）在保护肠道免受炎症方面发挥作用。我们在此研究了炎症性肠病（IBD）患者的肠道内源性大麻素系统，并研究了不可水解的 AEA 类似物甲酰胺（MAEA）对粘膜促炎反应的离体和体外作用。与非炎症性 IBD 粘膜相比，炎症性 IBD 粘膜中的 AEA 含量（而非 2-花生四烯酰甘油和 N-棕榈酰乙醇胺）明显降低，这与 AEA 合成酶 N-酰基磷脂酰乙醇胺特异性磷脂酶 D 的活性降低和 AEA 降解酶脂肪酸酰胺水解酶的活性升高相一致。MAEA 可显著下调器官培养活检和粘膜固有层单核细胞中干扰素-γ和肿瘤坏死因子-α的分泌。尽管这些结果很有希望，但仍需要进一步研究来确定大麻素途径在肠道炎症中的作用。
