Zeeh J M, Riley N E, Hoffmann P, Ruwe M, Goebell H, Gerken G, Dignass A U
Dept of Internal Medicine, University of Essen, Germany.
Scand J Gastroenterol. 2001 Jan;36(1):66-70. doi: 10.1080/00365520150218075.
Lymphocytes are widely believed to be responsible for persistent intestinal inflammation in inflammatory bowel diseases. Mycophenolate mofetil (MMF) is a potent immunosuppressant that inhibits lymphocyte proliferation and has been shown to be effective in preventing allograft rejection after organ transplantation. The purpose of this study was to assess the modulating effects of MMF on intestinal inflammation in an experimental model of colitis in rats.
Colitis was induced by rectal instillation of trinitrobenzenesulfonic acid (TNBS) in ethanol in male Sprague-Dawley rats. One group of rats (n = 10) was treated with MMF i.p. (25 mg/kg b.w.) daily for 1 week starting 24 h after induction of colitis. A second group of rats (n = 10) was treated with MMF at the same dose 2 days, I day and 1 h prior to induction of colitis. Control animals (n = 10) received vehicle only. After being killed, colonic tissue was macroscopically evaluated for necrosis and microscopically for ulcerations. Sections were stained and examined for the presence of granulocytes.
Administration of MMF after induction of TNBS colitis reduced macroscopic injury by 62% compared to control animals (P = 0.01). Microscopic ulcerations were reduced by 64% compared to controls (P = 0.009). In addition, posttreatment significantly reduced the number of granulocytes. MMF pretreatment did not significantly prevent macroscopic or microscopic tissue damage, or change the number of granulocytes.
Systemic administration of MMF significantly ameliorates tissue damage in a model of experimental colitis in rats suggesting that this compound may play an important role as an immunosuppressant in the therapy of inflammatory bowel diseases.
人们普遍认为淋巴细胞是炎症性肠病中持续性肠道炎症的病因。霉酚酸酯（MMF）是一种强效免疫抑制剂，可抑制淋巴细胞增殖，并已证明其在预防器官移植后同种异体移植排斥反应方面有效。本研究的目的是评估MMF对大鼠结肠炎实验模型中肠道炎症的调节作用。
通过向雄性Sprague-Dawley大鼠直肠内注入三硝基苯磺酸（TNBS）的乙醇溶液诱导结肠炎。一组大鼠（n = 10）在结肠炎诱导后24小时开始每天腹腔注射MMF（25 mg/kg体重），持续1周。另一组大鼠（n = 10）在结肠炎诱导前2天、1天和1小时接受相同剂量的MMF治疗。对照动物（n = 10）仅接受赋形剂。处死动物后，对结肠组织进行大体坏死评估和显微镜下溃疡评估。切片进行染色并检查粒细胞的存在情况。
与对照动物相比，TNBS诱导结肠炎后给予MMF可使大体损伤减少62%（P = 0.01）。与对照组相比，显微镜下溃疡减少64%（P = 0.009）。此外，治疗后显著减少了粒细胞数量。MMF预处理并未显著预防大体或显微镜下的组织损伤，也未改变粒细胞数量。
在大鼠实验性结肠炎模型中，全身给予MMF可显著改善组织损伤，表明该化合物可能在炎症性肠病治疗中作为免疫抑制剂发挥重要作用。
