乌梅丸对溃疡性结肠炎大鼠的治疗作用及其机制

目的观察乌梅丸对溃疡性结肠炎大鼠的治疗作用及对结肠黏膜组织中Toll样受体4（Toll-like receptor4,TLR4）、核因子κB（nuclear factor-kappa B,NF-κB）p65蛋白表达的影响。方法采用2,4-二硝基氯苯（2,4-dinitro-chlorobenzene,DNCB）加丙酮局部灌肠法建立溃疡性结肠炎（ulcerative colitis,UC）大鼠模型.将60只健康SD大鼠随机均分为正常（生理盐水）对照组、阳性对照组[柳氮磺胺吡啶（salazosulfapyridine,SASP）]、模型组、3个乌梅丸剂量组（0.575 g/kg、1.15 g/kg、2.3g/kg）,造模后给药15天,处死大鼠收集样本,观察结肠黏膜大体形态及组织学改变;应用免疫印迹（Western blot）法检测结肠黏膜组织中TLR4、NF-κB p65蛋白的表达水平。结果乌梅丸2.3 g/kg剂量组减轻了大鼠肠道水肿程度,并减少了赘生物及溃疡的形成,作用优于SASP组;模型组结肠黏膜组织TLR4、NF-κB p65蛋白的表达明现高于正常组（P〈0.01）,乌梅丸组和SASP组则低于模型组,其中乌梅丸2.3 g/kg剂量组尤其明显（P〈0.01）。结论乌梅丸对实验性大鼠溃疡性结肠炎有明显的治疗作用,其机制可能是通过抑制TLR4的表达,降低NF-κB p65的活性免疫调节,达到治疗目的。

Treatment Effects of Wumei Pill on Rats with Ulcerative Colitis and the Mechanisms

Objective To investigate the effects of Wumei pill on ulcerative colitis（UC） and Toll-like receptor 4（TLR4） and nuclear factor-kappa B（NF-κB） p65 expressions in the intestine mucosa of rats.Methods The UC rat model was established by using 2,4-dinitrochlorobenzene（DNCB） enema plus the acetone.Sixty healthy SD rats were randomly divided into normal control group,positive control group（sulfasalazine,SASP）,model group and Wumei pill group treated by three doses of Wumei pill（0.575 g/kg,1.15 g/kg and 2.3 g/kg respectively）.After establishing the UC model and treating the rats in treatment groups for 15 days,the rats were sacrificed.Samples were collected and the general form of the colonic mucosa and histological changes were observed.Western blot was employed to evaluate TLR4 and NF-κB p65 expressions in the colonic mucosa.Results In 2.3 g/kg Wumei pill group,the rats＇ intestinal edema was alleviated and the formation of the ulcer area was reduced compared with those in SASP group.TLR4 and NF-κB p65 expressions in the intestine mucosa in model group were much higher than those in normal group（P〈0.01）,lower in Wumei pill groups and SASP groups than those in the model group,especially in 2.3 g/kg Wumei pill group（P〈0.01）.Conclusion Wumei pill has a significant therapeutic effect on experimental ulcerative colitis in rats and the possible mechanisms refer to its inhibition on the expression of TLR4,and thereby reducing the activity of NF-κB p65.