Otto Loewi Research Center, Division of Pharmacology, Medical University of Graz, Graz, Austria.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Sci Rep. 2019 Feb 20;9(1):2358. doi: 10.1038/s41598-019-38865-4.
Preclinical studies have demonstrated that the endocannabinoid system (ECS) plays an important role in the protection against intestinal inflammation and colorectal cancer (CRC); however, human data are scarce. We determined members of the ECS and related components of the 'endocannabinoidome' in patients with inflammatory bowel disease (IBD) and CRC, and compared them to control subjects. Anandamide (AEA) and oleoylethanolamide (OEA) were increased in plasma of ulcerative colitis (UC) and Crohn's disease (CD) patients while 2-arachidonoylglycerol (2-AG) was elevated in patients with CD, but not UC. 2-AG, but not AEA, PEA and OEA, was elevated in CRC patients. Lysophosphatidylinositol (LPI) 18:0 showed higher levels in patients with IBD than in control subjects whereas LPI 20:4 was elevated in both CRC and IBD. Gene expression in intestinal mucosal biopsies revealed different profiles in CD and UC. CD, but not UC patients, showed increased gene expression for the 2-AG synthesizing enzyme diacylglycerol lipase alpha. Transcripts of CNR1 and GPR119 were predominantly decreased in CD. Our data show altered plasma levels of endocannabinoids and endocannabinoid-like lipids in IBD and CRC and distinct transcript profiles in UC and CD. We also report alterations for less known components in intestinal inflammation, such as GPR119, OEA and LPI.
临床前研究表明，内源性大麻素系统（ECS）在保护肠道炎症和结直肠癌（CRC）方面发挥着重要作用；然而，人类数据却很少。我们在炎症性肠病（IBD）和 CRC 患者中确定了 ECS 的成员以及“内源性大麻素组”的相关成分，并将其与对照受试者进行了比较。在溃疡性结肠炎（UC）和克罗恩病（CD）患者的血浆中，花生四烯酸乙醇酰胺（AEA）和油酰乙醇酰胺（OEA）增加，而 2-花生四烯酰甘油（2-AG）在 CD 患者中升高，但在 UC 患者中没有升高。2-AG 而不是 AEA、PEA 和 OEA 在 CRC 患者中升高。溶血磷脂酰肌醇（LPI）18:0 在 IBD 患者中的水平高于对照组，而 LPI 20:4 在 CRC 和 IBD 患者中均升高。肠黏膜活检的基因表达显示 CD 和 UC 之间存在不同的特征。只有 CD 患者，而不是 UC 患者，显示出 2-AG 合成酶二酰基甘油脂肪酶 alpha 的基因表达增加。CD 患者的 CNR1 和 GPR119 的转录本主要减少。我们的数据显示，IBD 和 CRC 患者的内源性大麻素和内源性大麻素样脂质的血浆水平发生了改变，UC 和 CD 之间存在不同的转录谱。我们还报告了在肠道炎症中较少被人所知的成分的改变，如 GPR119、OEA 和 LPI。
