Wolyniak M, Wlodarczyk M, Piscitelli F, Verde R, Di Marzo V, Mokrowiecka A, Malecka-Wojciesko E, Fabisiak A
Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland.
Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland.
J Physiol Pharmacol. 2024 Oct;75(5). doi: 10.26402/jpp.2024.5.08. Epub 2024 Dec 4.
The endocannabinoid system (ECS) and nociceptin receptor (NOP) have been implicated in the pathology of inflammatory bowel diseases (IBD) mediating pain and alleviating inflammation. In this study we searched for the possible activation of ECS and NOP system and the correlation between CB1, CB2 and NOP receptors in IBD patients. Patients diagnosed with IBDs who underwent colonic surgical resection or biopsy at colonoscopy and control group (patients without diagnosis of IBD, which colonoscopy for the different medical indications) were recruited into the study. In surgical specimen the quantification of endocannabinoids was obtained by liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry. In biopsy specimen, the expression of genes encoding CB1, CB2, and NOP receptors was determined with real-time RT-PCR. The relative expression of CB1 and CB2 receptors in human samples with IBD compared to the unrelated controls (HC) group was reduced compared to the controls, but no differences in relative expression of NOP receptor were detected. Statistical significance difference was reached only between the level of a relative expression of CB1 receptor in ulcerative colitis (UC) and HC groups (498 (57.45-1890) and 4946 (2098--12818) (P<0.05)). A statistically significant positive correlation between the relative expression of CB1 and NOP receptors (r=0.83, P<0.05) as well as CB2 and NOP receptors in Crohn's disease (CD) (r=0.87, P<0.05) was found. Several endocannabinoids were significantly (P<0.05) increased in tissue collected from UC and CD patients in comparison to controls. CB1 and CB2 but not NOP receptors were found to be downregulated in IBD. Correlation of CB1, CB2 and NOP expression may suggest their common roles and shared molecular pathways in CD. Upregulated level of several endocannabinoids may point out to their role in IBD. Their estimation may be possibly useful in IBD diagnostics.
内源性大麻素系统（ECS）和孤啡肽受体（NOP）与炎症性肠病（IBD）的病理过程有关，可介导疼痛并减轻炎症。在本研究中，我们探寻了IBD患者中ECS和NOP系统的可能激活情况以及CB1、CB2和NOP受体之间的相关性。招募了经结肠镜检查进行结肠手术切除或活检的IBD诊断患者以及对照组（未诊断为IBD的患者，因不同医疗指征接受结肠镜检查）纳入研究。在手术标本中，通过液相色谱-大气压化学电离-质谱法对内源性大麻素进行定量。在活检标本中，采用实时逆转录聚合酶链反应测定编码CB1、CB2和NOP受体的基因表达。与无关对照组（HC）相比，IBD患者样本中CB1和CB2受体的相对表达降低，但未检测到NOP受体相对表达的差异。仅在溃疡性结肠炎（UC）组和HC组中CB1受体相对表达水平之间达到统计学显著差异（498（57.45 - 1890）和4946（2098 - 12818）（P < 0.05））。在克罗恩病（CD）中发现CB1与NOP受体的相对表达之间存在统计学显著正相关（r = 0.83，P < 0.05）以及CB2与NOP受体之间存在正相关（r = 0.87，P < 0.05）。与对照组相比，从UC和CD患者收集的组织中几种内源性大麻素显著升高（P < 0.05）。发现IBD中CB1和CB2受体而非NOP受体下调。CB1、CB2和NOP表达的相关性可能表明它们在CD中的共同作用和共享分子途径。几种内源性大麻素水平上调可能表明它们在IBD中的作用。对它们的评估可能在IBD诊断中有用。
