肥大细胞及类胰蛋白酶在溃疡性结肠炎大鼠结肠黏膜中的表达  

Treatment with nafamostat mesilate reduces mast cell number and down-regulates tryptase expression in experimental ulcerative colitis in rats

作　　者：林艺娟[1,2] 王承党[1,2] 庄则豪[1,2] 范华[1,2] 黄循铷[1,2] 刘霞[1,2] 

机构地区：[1]福建医科大学附属第一医院消化内科 [2]福建医科大学消化系疾病研究室,福建省福州市350005

出　　处：《世界华人消化杂志》2011年第2期126-131,共6页World Chinese Journal of Digestology

摘　　要：目的:观察类胰蛋白酶抑制剂甲磺酸卡萘司他(NM)对肥大细胞(MC)数量和类胰蛋白酶表达及血清IL-6、IL-8含量的影响.方法:40只♂Wistar大鼠按1∶3随机分为空白对照组(A组)和研究组(S组),造模成功后S组再随机分为3组,并以不同溶液灌肠:B组(模型对照组,无菌蒸馏水)、C组(NM组,10-9mol/LNM)、D组[5-氨基水杨酸(5-ASA)组,100mg/kg5-ASA].以免疫组织化学方法检测远端结肠黏膜MC类胰蛋白酶的表达变化,以ELISA法检测动物血清中IL-6、IL-8的表达变化.结果:(1)治疗第1天,A组DAI评分与B、C、D组相比,差异有显著统计学意义(P<0.01);实验结束后,B组DAI、HI评分与C、D组相比明显增高(DAI:6.25±1.67vs3.63±1.30,2.75±0.71;HI:5.10±0.74vs2.30±0.67,2.00±0.82;均P<0.01);(2)B组远端结肠黏膜MC数显著高于C、D组(MC:13.25±1.67vs6.37±1.19,5.00±1.07,均P<0.05).B组类胰蛋白酶表达量显著低于C、D组(119.22±9.85vs150.83±10.06,140.60±8.93,均P<0.01);(3)B组血清IL-6、IL-8浓度显著高于C、D组(IL-6:83.32ng/L±7.90ng/L vs40.09ng/L±6.20ng/L,40.39ng/L±6.31ng/L;IL-8:232.41ng/L±18.72ng/L vs141.05ng/L±10.33ng/L,132.09ng/L±23.37ng/L;均P<0.01).以上各指标C组与D组比较无统计学差异,治疗效果相当.结论:小剂量类胰蛋白酶抑制剂可以下调结肠黏膜肥大细胞数量、抑制MC类胰蛋白酶表达,对DSS诱导溃疡性结肠炎大鼠有治疗作用.AIM： To investigate the effects of treatment with nafamostat mesilate （NM）, a tryptase inhibitor, on the number of mast cells （MCs） and the ex- pression of MC tryptase in the colonic mucosa of rats with dextran sulfate sodium （DSS）-induced ulcerative colitis. METHODS： Forty male Wistar rats were ran- domly divided into control group （group A, n = 10） and experimental group （n = 30）. After induction of colitis with DSS, the experimental group were further divided into three groups and intraintestinally given distilled water （group B）, 10.9 mol/L NM （group C） and 100 mg/kg 5-ASA （group D）, respectively. The expression of MC tryptase in the distal colonic mucosa was as- sessed by immunohistochemistry. Serum concen- trations of IL-6 and IL-8 were measured by ELISA. RESULTS： On day 1 after treatment, the dis- ease activity index （DAI） score in group B was significantly higher than those in groups C and D （both P 〈 0.01）. On day 7, the DAI （6.25 ± 1.67 vs 3.63 ± 1.3, 2.75 ± 0.71, both P 〈 0.01） and his- tological index （HI） scores （5.10 ± 0.74 vs 2.30 ± 0.67, 2.00 ± 0.82; both P 〈 0.01） in group B were significantly higher than those in groups C and D. The number of mast cells （13.25 ± 1.67 vs 6.37 ± 1.19, 5.00 ± 1.07, both P 〈 0.01） and average gray scale （AGS） for MC tryptase staining （119.22 ± 9.85 vs 140.60 ± 8.93,150.83 ± 10.06, both P 〈 0.01） in the colonic mucosa in group B showed signifi- cant differences with those in groups C and D. The levels of serum IL-6 （83.32 ± 7.90 vs 40.09 ± 6.20, 40.39 ± 6.31, both P 〈 0.01） and IL-8 （232.41 ± 18.72 vs 141.05 ± 10.33, 132.09 ± 23.37, both P 〈 0.01） in group B were significantly higher than those in groups C and D. No significant differ- ences were found in the above parameters be- tween groups C and D （all P 〉 0.05）. CONCLUSION： Small-dosage nafamostat mesi- late can reduce mast cell number and down-reg- ulate tryptase expression in the colonic mucosa

关 键 词：葡聚糖硫酸钠 溃疡性结肠炎 肥大细胞 类胰蛋白酶 类胰蛋白酶抑制剂 白介素6 白介素8 

分 类 号：R574.62[医药卫生—消化系统]