乌司他丁对大鼠实验性溃疡性结肠炎的作用

摘要

目的 探讨乌司他丁对大鼠实验性溃疡性结肠炎(UC)的作用及机制.方法 120只SD大鼠随机分为4组,每组各30只.使用三硝基苯磺酸钠( TNBS)建立UC模型,Ⅰ组不使用乌司他丁,为造膜对照组；Ⅱ、Ⅲ、Ⅳ组分别于造模0、6、12 h使用乌司他丁,剂量为2万单位/kg,为研究组.检测分析各组肠静脉内毒素、肿瘤坏死因子α(TNF-α)和UC模型症状积分(实验开始24、72、168 h各观察10只大鼠).结果 ①在实验各时段,使用乌司他丁组UC大鼠病变积分均低于Ⅰ组(均P＜0.05),且24、72 h时Ⅱ、Ⅲ、Ⅳ组差异均有统计学意义[24 h:(1.8±0.4),(2.7±0.3),(3.0±0.1)；72 h:(3.7±2.3),(4.2±1.2),(5.0±0.9),均P＜0.05],但168 h时Ⅱ、Ⅲ、Ⅳ组未见明显差异.②使用乌司他丁组肠静脉内毒素含量在实验各时期内均低于Ⅰ组,24h时Ⅱ组与Ⅲ组、Ⅳ组之间差异均有统计学意义[(97.7±11.7) ng/L比(117.1±9.7) ng/L,( 124.3 ±4.9) ng/L,均P＜0.05],72、168 h时Ⅱ、Ⅲ、Ⅳ组肠静脉血内毒素含量差异无统计学意义.③24h时Ⅱ组TNF-α低于Ⅰ组及Ⅲ、Ⅳ组[(6.7±2.6) pg/100 μg比(13.5±1.7),(11.8±2.8),(12.4±2.7)pg/100 μg,均P＜0.05)],但72、168 h使用乌司他丁各组低于Ⅰ组.结论 乌司他丁对TNBS导致的大鼠UC有明显防护作用,其机制可能通过抑制内毒素水平而降低免疫异常水平.%Objective To investigate the effect of ulinastatin on ulcerative colitis of rats.Methods One hundred and twenty sprague dawley (S-D)rats were divided into four groups randomly. Ulcerative colitis (UC)model was induced by three nitrobenzene sulfonate (TNBS). The group Ⅰ was control group and was free of ulinastatin;group Ⅱ,Ⅲ,Ⅳ were given ulinastatin [ 2 × 105 u/(kg· 12 h)] at 0,6,12 h after TNBS.Endotoxin,tumor necrosis factor (TNF)-α of Intestinal vein and UC symptomatic index were detected and analyzed.Results ①UC symptomatic index in given ulinastatin groups was lower than that in Ⅰ group at any stage (P＜0.05 )and showed statistical differences among group Ⅱ and Ⅲ,Ⅳ＜0.05 )at 24 h and 72 h.②Endotoxin in ulinastatin groups was lower compared to that in control group(P＜0.05 ).③ There was a lower TNF-α level in group Ⅱcompared to other groups (P ＜0.05);at 72 h,168 h,TNF-α in ulinastatin groups was lower than that in group Ⅰ (P＜0.05).Conclusion Ulinastatin shows good effects on rats UC caused by TNBS.It may depress abnormal immune reaction through inhibiting endotoxin.