State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, People's Republic of China.
Free Radic Biol Med. 2011 Jan 15;50(2):228-36. doi: 10.1016/j.freeradbiomed.2010.10.703. Epub 2010 Oct 26.
Reactive oxygen species (ROS) exhibit a key role in the pathogenesis of inflammatory bowel disease (IBD). 3,3'-Diindolylmethane (DIM) can protect against oxidative stress in a breast cancer susceptibility gene 1 (BRCA1)-dependent manner. The aim of this study was to examine the therapeutic effects of DIM in experimental colitis and investigate the possible mechanisms underlying its effects on intestinal inflammation. The therapeutic effects of DIM were studied in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Pathological markers of colitis severity, antioxidant activity, and ROS generation in colonic tissue were measured. The impact of DIM on ROS-induced endothelial vascular cell adhesion molecule 1 (VCAM-1) expression and leukocyte-endothelial cell interaction was further investigated in cultures of endothelial cells and in the TNBS-induced colitis model. Administration of DIM was demonstrated to attenuate experimental colitis, as judged by pathological indices. DIM could effectively stimulate the expression of BRCA1 in vitro and in vivo and reduce ROS generation, leading to the inhibition of VCAM-1 expression and leukocyte-endothelial cell adhesion, and finally resulted in an alleviation of experimental colitis. DIM has shown anti-IBD activity in animal models by inhibiting ROS-induced VCAM-1 expression and leukocyte recruitment via a BRCA1-dependent antioxidant pathway and thus may offer potential treatments for IBD patients.
活性氧（ROS）在炎症性肠病（IBD）的发病机制中起关键作用。3,3'-二吲哚甲烷（DIM）可以通过乳腺癌易感基因 1（BRCA1）依赖性方式保护对抗氧化应激。本研究旨在研究 DIM 在实验性结肠炎中的治疗作用，并探讨其对肠道炎症影响的可能机制。采用 2,4,6-三硝基苯磺酸（TNBS）诱导结肠炎研究 DIM 的治疗效果。测量了结肠炎严重程度的病理标志物、抗氧化活性和结肠组织中的 ROS 生成。进一步研究了 DIM 对 ROS 诱导的内皮血管细胞粘附分子 1（VCAM-1）表达和白细胞-内皮细胞相互作用的影响，在体外培养的内皮细胞和 TNBS 诱导的结肠炎模型中进行了研究。研究表明，DIM 的给药可通过病理指数减轻实验性结肠炎。DIM 可以在体外和体内有效地刺激 BRCA1 的表达，并减少 ROS 的产生，从而抑制 VCAM-1 的表达和白细胞-内皮细胞的粘附，最终导致实验性结肠炎的缓解。DIM 通过抑制 ROS 诱导的 VCAM-1 表达和白细胞募集，通过 BRCA1 依赖性抗氧化途径发挥抗 IBD 活性，因此可能为 IBD 患者提供潜在的治疗方法。
