Seibel Jan, Molzberger Almut F, Hertrampf Torsten, Laudenbach-Leschowski Ute, Degen Gisela H, Diel Patrick
Department of Molecular and Cellular Sports Medicine, DSHS Cologne, Am Sportpark Müngersdorf, 50933 Cologne, Germany.
Arch Toxicol. 2008 Dec;82(12):941-50. doi: 10.1007/s00204-008-0309-7. Epub 2008 May 27.
Inflammatory bowel disease (IBD) is very common in Europe and USA. Its incidence in East Asia has been traditionally low, albeit the risk of IBD increases in Asian immigrants adopting western lifestyles, suggesting a strong role of environmental/dietary factors in IBD. A lifelong exposure to phytoestrogen-rich diets has been associated with a decreased risk of developing breast cancer and might also be protective against IBD. We studied the influence of in utero and postnatal exposure to a phytoestrogen (PE)-rich diet on acute inflammation in an animal model of TNBS-induced colitis. Wistar rats were exposed in utero and postnatally to high (genistein: 240 microg/g feed; daidzein: 232 microg/g feed) or very low levels (genistein and daidzein <10 microg/g feed) of phytoestrogen isoflavones fed to pregnant dams with the diet and throughout nursing. After weaning, the offspring had free access to these diets. At the age of 11 weeks, colitis was induced with an enema of TNBS. After 3 days, animals were sacrificed and tissues were collected for histological evaluation and analysis of molecular markers of inflammation. Animals kept on a PE-rich diet (PRD) had higher colon weights than animals on low PE-levels (PDD), suggesting enhanced acute inflammation by phytoestrogens. This result was supported by histological findings and by analysis of myeloperoxidase activity. Interestingly, relative mRNA and protein expression of cyclooxygenase-2 (COX-2) were modulated in rats on PRD, providing evidence that COX-2, the inducible isoform of the enzyme, is involved in the management of colonic inflammation. Our results suggest that early-in-life exposure to PE might not protect against the development of IBD but enhances the extent of acute inflammation.
炎症性肠病（IBD）在欧洲和美国非常常见。传统上，其在东亚的发病率较低，尽管采用西方生活方式的亚洲移民患IBD的风险会增加，这表明环境/饮食因素在IBD中起着重要作用。终生食用富含植物雌激素的饮食与患乳腺癌风险降低有关，并且可能对IBD也有保护作用。我们研究了在子宫内和出生后暴露于富含植物雌激素（PE）的饮食对三硝基苯磺酸（TNBS）诱导的结肠炎动物模型急性炎症的影响。将Wistar大鼠在子宫内和出生后暴露于高剂量（染料木黄酮：240微克/克饲料；大豆苷元：232微克/克饲料）或极低剂量（染料木黄酮和大豆苷元<10微克/克饲料）的植物雌激素异黄酮，在孕期和整个哺乳期给怀孕的母鼠喂食这种饲料。断奶后，后代可自由获取这些饮食。在11周龄时，用TNBS灌肠诱导结肠炎。3天后，处死动物并收集组织进行组织学评估和炎症分子标志物分析。食用富含PE饮食（PRD）的动物的结肠重量高于低PE水平（PDD）的动物，这表明植物雌激素增强了急性炎症。组织学结果和髓过氧化物酶活性分析支持了这一结果。有趣的是，PRD组大鼠中环氧合酶-2（COX-2）的相对mRNA和蛋白表达受到调节，这证明该酶的诱导型同工酶COX-2参与了结肠炎症的调控。我们的结果表明，生命早期暴露于PE可能无法预防IBD的发生，反而会加重急性炎症的程度。
