Playford R J, MacDonald C E, Calnan D P, Floyd D N, Podas T, Johnson W, Wicks A C, Bashir O, Marchbank T
Department of Gastroenterology, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W120NN, UK.
Clin Sci (Lond). 2001 Jun;100(6):627-33.
Non-steroidal anti-inflammatory drugs (NSAIDs) are effective analgesics but cause gastrointestinal injury. Present prophylactic measures are suboptimal and novel therapies are required. Bovine colostrum is a cheap, readily available source of growth factors, which reduces gastrointestinal injury in rats and mice. We therefore examined whether spray-dried, defatted colostrum could reduce the rise in gut permeability (a non-invasive marker of intestinal injury) caused by NSAIDs in volunteers and patients taking NSAIDs for clinical reasons. Healthy male volunteers (n=7) participated in a randomized crossover trial comparing changes in gut permeability (lactulose/rhamnose ratios) before and after 5 days of 50 mg of indomethacin three times daily (tds) per oral with colostrum (125 ml, tds) or whey protein (control) co-administration. A second study examined the effect of colostral and control solutions (125 ml, tds for 7 days) on gut permeability in patients (n=15) taking a substantial, regular dose of an NSAID for clinical reasons. For both studies, there was a 2 week washout period between treatment arms. In volunteers, indomethacin caused a 3-fold increase in gut permeability in the control arm (lactulose/rhamnose ratio 0.36+/-0.07 prior to indomethacin and 1.17+/-0.25 on day 5, P<0.01), whereas no significant increase in permeability was seen when colostrum was co-administered. In patients taking long-term NSAID treatment, initial permeability ratios were low (0.13+/-0.02), despite continuing on the drug, and permeability was not influenced by co-administration of test solutions. These studies provide preliminary evidence that bovine colostrum, which is already currently available as an over-the-counter preparation, may provide a novel approach to the prevention of NSAID-induced gastrointestinal damage in humans.
非甾体抗炎药(NSAIDs)是有效的镇痛药,但会导致胃肠道损伤。目前的预防措施并不理想,需要新的治疗方法。牛初乳是一种廉价且易于获得的生长因子来源,可减轻大鼠和小鼠的胃肠道损伤。因此,我们研究了喷雾干燥、脱脂的初乳是否能降低因临床原因服用NSAIDs的志愿者和患者中NSAIDs引起的肠道通透性升高(肠道损伤的一种非侵入性标志物)。健康男性志愿者(n = 7)参与了一项随机交叉试验,比较每日三次口服50 mg消炎痛(tds)5天前后,同时服用初乳(125 ml,tds)或乳清蛋白(对照)时肠道通透性(乳糖/鼠李糖比率)的变化。第二项研究考察了初乳溶液和对照溶液(125 ml,tds,共7天)对因临床原因长期大量规律服用NSAIDs的患者(n = 15)肠道通透性的影响。两项研究中,不同治疗组之间均有2周的洗脱期。在志愿者中,消炎痛使对照组的肠道通透性增加了3倍(消炎痛治疗前乳糖/鼠李糖比率为0.36±0.07,第5天为1.17±0.25,P<0.01),而同时服用初乳时通透性未见显著增加。在长期服用NSAIDs治疗的患者中,尽管持续用药,但初始通透性比率较低(0.13±0.02),且测试溶液的共同给药对通透性没有影响。这些研究提供了初步证据,表明目前已有非处方制剂的牛初乳可能为预防人类NSAIDs诱导的胃肠道损伤提供一种新方法。