Thomas M G, Nugent K P, Forbes A, Williamson R C
Royal Postgraduate Medical School, Hammersmith Hospital, London.
Gut. 1994 Dec;35(12):1718-20. doi: 10.1136/gut.35.12.1718.
Vitamin D3 reduces human rectal crypt cell production rate (CCPR) and may thereby protect against colorectal cancer. Cell turnover is increased in ulcerative proctocolitis, which might therefore respond to vitamin D3 metabolites. This study investigated the effect of calcipotriol, a synthetic vitamin D3 analogue that avoids hypercalcaemia, on human rectal CCPR in ulcerative proctocolitis. Paired rectal biopsy specimens from seven patients with severe disease were established in organ culture with or without calcipotriol (1 x 10(-6) M). After 15 hours, vincristine (0.6 microgram/ml) was added to induce metaphase arrest, and CCPR was determined by linear regression analysis of accumulated metaphases. Compared with values in 17 controls with incidental anal conditions, median rectal CCPR was 28% higher in ulcerative proctocolitis: 5.90 (5.00-9.50) v 4.80 (2.85-7.07) cells/crypt/hour (p < 0.01). Calcipotriol reduced CCPR by 62% in patients with ulcerative proctocolitis, from 5.90 (5.00-9.50) to 2.21 (0.81-3.22) cells/crypt/hour (median with range) p < 0.01. Thus calcipotriol can dampen the hyperproliferative state in ulcerative proctocolitis and could have a therapeutic role in the control of this inflammatory condition.
维生素D3可降低人类直肠隐窝细胞生成率(CCPR),从而可能预防结直肠癌。溃疡性直肠结肠炎患者的细胞更新加快,因此可能对维生素D3代谢产物有反应。本研究调查了骨化三醇(一种可避免高钙血症的合成维生素D3类似物)对溃疡性直肠结肠炎患者直肠CCPR的影响。将7例重症患者的配对直肠活检标本置于含或不含骨化三醇(1×10⁻⁶ M)的器官培养液中培养。15小时后,加入长春新碱(0.6微克/毫升)诱导细胞中期停滞,通过对累积中期细胞进行线性回归分析来测定CCPR。与17例因肛门疾病偶然接受检查的对照者相比,溃疡性直肠结肠炎患者的直肠CCPR中位数高28%:分别为5.90(5.00 - 9.50)和4.80(2.85 - 7.07)个细胞/隐窝/小时(p < 0.01)。骨化三醇使溃疡性直肠结肠炎患者的CCPR降低了62%,从5.90(5.00 - 9.50)降至2.21(0.81 - 3.22)个细胞/隐窝/小时(中位数及范围),p < 0.01。因此,骨化三醇可抑制溃疡性直肠结肠炎的过度增殖状态,在控制这种炎症性疾病方面可能具有治疗作用。