Department of Gastroenterology, Peking University People's Hospital, Beijing, China.
Eur J Gastroenterol Hepatol. 2009 Oct;21(10):1145-52. doi: 10.1097/MEG.0b013e32830edb29.
To analyze the therapeutic effect of oral tolerance and nasal tolerance singly and in combination with mucosal adjuvant on experimental colitis in rats.
Rat models were established using trinitrobenzenesulphonic acid enemas. Ovalbumin was used as inducing antigen and lipopolysaccharide as adjuvant. Colonic scores, splenic mononuclear cell proliferation, and expressions of Toll-like receptors (TLR) and regulatory T cells were determined.
Colonic scores decreased most significantly after ovalbumin and lipopolysaccharide nasal administration (P<0.05). Colonic expression of forkhead box P3 in rats after ovalbumin and lipopolysaccharide oral (P<0.05) and nasal administration (P<0.01) were both significantly higher than untreated rats. TLR2 expression on CD4(+)CD25(+) T cells decreased most significantly after ovalbumin and lipopolysaccharide nasal therapies (P<0.01). TLR4 colonic expression decreased significantly after ovalbumin and lipopolysaccharide oral administration (P<0.05) and lipopolysaccharide oral administration (P<0.05).
Although experimental colitis prevented oral tolerance, nasal tolerance was successfully induced. The therapeutic effect of nasal tolerance combined with adjuvant produced the best results. TLR downregulation and CD4(+)CD25(+) T cells upregulation were involved in mucosal tolerance.
分析口服耐受和鼻内耐受单独及联合黏膜佐剂对实验性结肠炎大鼠的治疗作用。
采用三硝基苯磺酸灌肠法建立大鼠模型。卵清蛋白作为诱导抗原，脂多糖作为佐剂。测定结肠评分、脾单核细胞增殖以及 Toll 样受体（TLR）和调节性 T 细胞的表达。
卵清蛋白和脂多糖鼻内给药后结肠评分下降最明显（P<0.05）。卵清蛋白和脂多糖口服（P<0.05）和鼻内给药（P<0.01）后大鼠结肠中叉头框 P3 的表达均明显高于未处理组。CD4(+)CD25(+)T 细胞上 TLR2 的表达在卵清蛋白和脂多糖鼻内治疗后下降最明显（P<0.01）。TLR4 在结肠中的表达在卵清蛋白和脂多糖口服给药后明显下降（P<0.05），脂多糖口服给药后也明显下降（P<0.05）。
虽然实验性结肠炎预防了口服耐受，但成功诱导了鼻内耐受。鼻内耐受联合佐剂的治疗效果最佳。TLR 下调和 CD4(+)CD25(+)T 细胞上调参与黏膜耐受。
