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目的:研究地塞米松(DX)-右旋糖酐(500000)连接物(DXD50)在大鼠胃肠道的转运及其对大鼠溃疡性结肠炎的疗效。方法:将DXD50给大鼠ig,监测该DXD50在大鼠胃肠道不同部位释放DX的动力学过程及血药浓度变化。用三硝基苯磺酸诱导大鼠溃疡性结肠炎,以结肠溃疡面积、结肠重量、结肠组织髓过氧化物酶、大鼠外周血淋巴细胞数、胸腺及脾脏重量为指标,观察连接物的疗效。结果:口服连接物后,DX主要分布在盲肠和结肠中。DXD50及DX0.25μmol·kg~(-1)·d~(-1)可分别使大鼠溃疡面积缩小55.6％和33.3％,同时结肠重量下降17.9％和2.6％。DXD50 0.25μmol·kg~(-1)·d~(-1)对大鼠外周血淋巴细胞数、胸腺及脾脏重量无影响,而同等剂量的DX可引起大鼠外周血淋巴细胞数、胸腺及脾脏重量明显下降(P<0.05 vs control)。结论:DXD50可将DX特异地转运到结肠,它是一种有潜力的治疗炎症性肠病药物。
OBJECTIVE: To study the transport of dexamethasone (DX) -dextran (500000) conjugate (DXD50) in the gastrointestinal tract of rats and its effect on ulcerative colitis in rats. METHODS: DXD50 was given to rats and the kinetics and plasma concentrations of DXD released in different parts of the gastrointestinal tract of rats were monitored. Trinitrobenzene sulfonic acid was used to induce ulcerative colitis in rats. Colon ulcer area, colon weight, colony myeloperoxidase, peripheral blood lymphocyte count, thymus and spleen weights were used as indicators to observe the effects of Efficacy. Results: DX was mainly distributed in the cecum and colon after oral attachment. DXD50 and DX0.25μmol · kg -1 d -1 reduced the area of ulcer in rats by 55.6% and 33.3%, respectively, while the colon weights decreased by 17.9% and 2.6% respectively. DXD50 0.25μmol · kg -1 · d -1 had no effect on the number of peripheral blood lymphocytes, thymus and spleen in rats, while the same dosage of DX could cause the number of peripheral blood lymphocytes, thymus, Spleen weight decreased significantly (P <0.05 vs control). CONCLUSIONS: DXD50 specifically translocates DX to the colon, a potential drug for inflammatory bowel disease.