Ochsenkühn Thomas, Marsteller Igor, Hay Ulrich, Diebold Joachim, Paumgartner Gustav, Göke Burkhard, Sackmann Michael
Department of Medicine II, Klinikum Grosshadern, Munich, Germany.
Digestion. 2003;68(4):209-16. doi: 10.1159/000075927. Epub 2003 Dec 30.
In animal models ursodeoxycholic acid (UDCA) showed a chemoprotective effect against colon cancer. To explain this, a reduced proliferation of the colorectal mucosal proliferation was suggested. We, therefore, examined the influence of UDCA on the proliferation of normal colorectal mucosa in humans.
Following endoscopic polypectomy, 20 patients with colorectal adenomas were randomized to receive either UDCA (750 mg/day, n = 10, group A) or placebo (n = 10, group B) for 6 months in a double-blinded way. Colorectal biopsies were sampled before and at the end of the medication by total colonoscopy. Colorectal mucosal proliferation was measured by FACScan analysis of propidium iodine labeling. Serum was sampled, and serum bile acids were analyzed by gas chromatography.
The proliferation rates at the end of the study were similar in both groups (median 15.4%; range 12.0-20.9 in group A; median 16.0%, 14.0-20.2 in group B, p = 0.41). Serum lithocholic acid levels at the end of the study were significantly higher in group A (1.3 micromol/l, 0.9-1.8) than in group B (0.7 micromol/l, 0-1.7, p < 0.02), whereas serum deoxycholic acid levels were similar in both groups.
In this study, UDCA treatment for 6 months does not seem to induce changes in the proliferative behavior of the colorectal mucosa in patients with adenomas. It seems likely that a putative chemopreventive effect of UDCA in humans is not exerted by a reduction of the colorectal proliferation.
在动物模型中，熊去氧胆酸（UDCA）对结肠癌显示出化学保护作用。为了解释这一点，有人提出大肠黏膜增殖会减少。因此，我们研究了UDCA对人正常大肠黏膜增殖的影响。
在内镜下息肉切除术后，将20例大肠腺瘤患者随机分为两组，双盲接受UDCA（750毫克/天，n = 10，A组）或安慰剂（n = 10，B组）治疗6个月。在用药前及用药结束时通过全结肠镜检查采集大肠活检样本。通过碘化丙啶标记的流式细胞仪分析测量大肠黏膜增殖情况。采集血清，通过气相色谱法分析血清胆汁酸。
研究结束时两组的增殖率相似（A组中位数为15.4%；范围为12.0 - 20.9；B组中位数为16.0%，14.0 - 20.2，p = 0.41）。研究结束时A组血清石胆酸水平（1.3微摩尔/升，0.9 - 1.8）显著高于B组（0.7微摩尔/升，0 - 1.7，p < 0.02），而两组血清脱氧胆酸水平相似。
在本研究中，UDCA治疗6个月似乎并未引起腺瘤患者大肠黏膜增殖行为的改变。UDCA在人体中的假定化学预防作用似乎并非通过减少大肠增殖来实现。
