Buecher Bruno, Thouminot Cécile, Menanteau Jean, Bonnet Christian, Jarry Anne, Heymann Marie-Françoise, Cherbut Christine, Galmiche Jean-Paul, Blottière Hervé M
Centre de Recherche en Nutrition Humaine de Nantes, INSERM U539, CHU Hôtel-Dieu, 44035 Nantes, France.
Reprod Nutr Dev. 2003 Jul-Aug;43(4):347-56. doi: 10.1051/rnd:2003028.
According to Burkitt's hypothesis, dietary fibres may protect against the development of colorectal cancer. In rats, studies have shown that only butyrate-producing fibres are protective. In parallel, in humans, non-steroidal anti-inflammatory drugs, which target cyclooxygenases, have been shown to display a protective effect against colorectal cancer. Among them, COX-2-selective inhibitors which present less side effects than non-selective agents, are promising as chemopreventive agents. Our aim was to analyse the effect of an association between butyrate-producing fibres and the COX-2 inhibitor on the development of aberrant crypt foci (ACF) in rats. Fisher F344 rats were fed with (1) a standard low fibre control diet; (2) the standard diet supplemented with 1500 ppm celecoxib; (3) a diet supplemented with 6% fructo-oligosaccharide (FOS); and (4) a diet with both celecoxib and FOS. Three weeks later, the rats were injected twice with azoxymethane and the number of ACF was determined 15 weeks later. In the control group, 43.8 +/- 6.4 ACF were found. This number was not significantly modified by the addition of FOS or celecoxib alone to the diet. However, the association of FOS and celecoxib resulted in a 61% reduction in the number of ACF (P < 0.01). The number of aberrant crypt per foci was also reduced. Thus, although no significant effect of celecoxib or FOS alone was identified, the association of butyrate-producing fibre and celecoxib was effective in preventing the development of ACF. This preliminary study argues for a strong protective effect of such an association which deserves further studies.
根据伯基特假说,膳食纤维可能预防结直肠癌的发生。在大鼠实验中,研究表明只有产生丁酸盐的纤维具有保护作用。与此同时,在人类中,靶向环氧化酶的非甾体抗炎药已被证明对结直肠癌有保护作用。其中,副作用比非选择性药物少的COX - 2选择性抑制剂有望作为化学预防剂。我们的目的是分析产生丁酸盐的纤维与COX - 2抑制剂联合使用对大鼠异常隐窝灶(ACF)形成的影响。将Fisher F344大鼠分为四组喂养:(1)标准低纤维对照饮食;(2)添加1500 ppm塞来昔布的标准饮食;(3)添加6%低聚果糖(FOS)的饮食;(4)同时含有塞来昔布和FOS的饮食。三周后,给大鼠两次注射氧化偶氮甲烷,并在15周后测定ACF的数量。在对照组中,发现有43.8±6.4个ACF。单独在饮食中添加FOS或塞来昔布,这个数量没有明显改变。然而,FOS和塞来昔布联合使用使ACF数量减少了61%(P<0.01)。每个病灶的异常隐窝数量也减少了。因此,虽然单独使用塞来昔布或FOS没有显著效果,但产生丁酸盐的纤维与塞来昔布联合使用对预防ACF的形成是有效的。这项初步研究表明这种联合使用具有很强的保护作用,值得进一步研究。