Bjarnason I, Zanelli G, Prouse P, Williams P, Gumpel M J, Levi A J
Drugs. 1986;32 Suppl 1:35-41. doi: 10.2165/00003495-198600321-00007.
The suggestion that the intestinal mucosa may be abnormally permeable and thus a site of antigen absorption in rheumatoid arthritis was tested by a 51Cr EDTA intestinal permeability test. Twelve patients with rheumatoid arthritis untreated by non-steroidal anti-inflammatory drugs (NSAIDs) had normal test results, while 12 NSAID-treated patients had increased intestinal permeability. Ten volunteers ingested aspirin, ibuprofen and indomethacin 8 and 1 hours before the study. The increased intestinal permeability was proportional to drug potency to inhibit cyclo-oxygenase. Intestinal permeability also increased following an indomethacin suppository, which suggests that the effect is systemically mediated. 111Indium leucocyte scintigrams and faecal collection showed no evidence of intestinal inflammation in 9 patients untreated by NSAIDs. Twenty-nine of 53 NSAID-treated patients showed abnormal localisation of 111indium in the right iliac fossa at 20 hours, and 32 of 49 patients had increased faecal excretion of 111indium. A 99mTc-porphyrin scan suggested that the main site of NSAID-induced intestinal inflammation was the small bowel. NSAIDs are thus shown to disrupt intestinal integrity and long term treatment leads to inflammation of the small intestine.
采用51Cr EDTA肠道通透性试验，对类风湿关节炎患者肠道黏膜可能存在异常通透性，进而成为抗原吸收部位这一假说进行了验证。12例未使用非甾体抗炎药（NSAIDs）治疗的类风湿关节炎患者试验结果正常，而12例接受NSAIDs治疗的患者肠道通透性增加。10名志愿者在研究前8小时和1小时服用了阿司匹林、布洛芬和吲哚美辛。肠道通透性增加与药物抑制环氧化酶的效力成正比。吲哚美辛栓剂给药后肠道通透性也增加，这表明该效应是由全身介导的。9例未接受NSAIDs治疗的患者，111铟白细胞闪烁扫描和粪便收集结果均未显示肠道炎症迹象。53例接受NSAIDs治疗的患者中，29例在20小时时右髂窝111铟定位异常，49例患者中有32例粪便中111铟排泄增加。99m锝卟啉扫描显示，NSAIDs引起的肠道炎症主要部位是小肠。因此，NSAIDs可破坏肠道完整性，长期治疗会导致小肠炎症。
