Leinwand Kristina L, Gerich Mark E, Hoffenberg Edward J, Collins Colm B
*Children's Hospital Colorado, Department of Pediatrics, Digestive Health Institute, Aurora, Colorado; †Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado; and ‡Division of Gastroenterology and Hepatology, University of Colorado, Aurora, Colorado.
Inflamm Bowel Dis. 2017 Feb;23(2):192-199. doi: 10.1097/MIB.0000000000001004.
Inflammatory bowel disease (IBD) is a lifelong disease of the gastrointestinal tract whose annual incidence and prevalence is on the rise. Current immunosuppressive therapies available for treatment of IBD offer limited benefits and lose effectiveness, exposing a significant need for the development of novel therapies. In the clinical setting, cannabis has been shown to provide patients with IBD symptomatic relief, although the underlying mechanisms of their anti-inflammatory effects remain unclear.
This review reflects our current understanding of how targeting the endocannabinoid system, including cannabinoid receptors 1 and 2, endogenous cannabinoids anandamide and 2-arachidonoylglycerol, atypical cannabinoids, and degrading enzymes including fatty acid amide hydrolase and monoacylglycerol lipase, impacts murine colitis. In addition, the impact of cannabinoids on the human immune system is summarized.
Cannabinoid receptors 1 and 2, endogenous cannabinoids, and atypical cannabinoids are upregulated in inflammation, and their presence and stimulation attenuate murine colitis, whereas cannabinoid receptor antagonism and cannabinoid receptor deficient models reverse these anti-inflammatory effects. In addition, inhibition of endocannabinoid degradation through monoacylglycerol lipase and fatty acid amide hydrolase blockade can also attenuate colitis development, and is closely linked to cannabinoid receptor expression.
Although manipulation of the endocannabinoid system in murine colitis has proven to be largely beneficial in attenuating inflammation, there is a paucity of human study data. Further research is essential to clearly elucidate the specific mechanisms driving this anti-inflammatory effect for the development of therapeutics to target inflammatory disease such as IBD.
炎症性肠病（IBD）是一种终身性胃肠道疾病，其年发病率和患病率呈上升趋势。目前可用于治疗IBD的免疫抑制疗法益处有限且会失效，这凸显了开发新疗法的迫切需求。在临床环境中，大麻已被证明可为IBD患者提供症状缓解，但其抗炎作用的潜在机制仍不清楚。
本综述反映了我们目前对靶向内源性大麻素系统如何影响小鼠结肠炎的理解，该系统包括大麻素受体1和2、内源性大麻素花生四烯乙醇胺和2-花生四烯酸甘油酯、非典型大麻素以及包括脂肪酸酰胺水解酶和单酰甘油脂肪酶在内的降解酶。此外，还总结了大麻素对人体免疫系统的影响。
大麻素受体1和2、内源性大麻素以及非典型大麻素在炎症中上调，它们的存在和刺激可减轻小鼠结肠炎，而大麻素受体拮抗作用和大麻素受体缺陷模型则会逆转这些抗炎作用。此外，通过单酰甘油脂肪酶和脂肪酸酰胺水解酶阻断抑制内源性大麻素降解也可减轻结肠炎的发展，并且与大麻素受体表达密切相关。
尽管在小鼠结肠炎中对内源性大麻素系统的调控已被证明在减轻炎症方面大体上是有益的，但人体研究数据却很少。进一步的研究对于明确阐明驱动这种抗炎作用的具体机制至关重要，以便开发针对IBD等炎症性疾病的治疗方法。
