NBD多肽治疗实验性溃疡性结肠炎的时-效关系  

Time-effection relationship of micromolecule polypeptide combining with NEMO-binding domain treating for rats of ulcerative colitis

作　　者：崔淑兰[1] 杨剑[2] 陈垦[2] 王晖[3] 龙友明[2] 王念林[2] 谢文瑞[2] 刘君君[2] 

机构地区：[1]广东药学院附属门诊部内科,广东广州510224 [2]广东药学院临床医学院,广东广州510310 [3]广东药学院中药学院,广东广州510006

出　　处：《中国医院药学杂志》2009年第23期1986-1989,共4页Chinese Journal of Hospital Pharmacy

基　　金：广东省医学科研基金项目(编号:A2005325)

摘　　要：目的:观察核因子κB必需分子(NEMO)结合的小分子多肽(NBD多肽)对实验性大鼠溃疡性结肠炎治疗作用的时效关系。方法:64只SD大鼠随机分成3d组、7d组,采用三硝基苯磺酸(TNBS)灌肠法制作溃疡性结肠炎大鼠模型,予腹腔注射1.3mg/100g NBD多肽评估炎症活动指数(IAI)评分,按照给药后3,7d分别处死各组的动物取结肠,肉眼观察结肠黏膜病变且按损伤情况积分,行病理切片、苏木素伊红(hematoxylin eosin,HE)染色,光镜下评估组织损伤,取病变结肠组织切片行免疫组化检测核因子κB(NF-κB)表达,其上清用相应试剂盒检测髓过氧化物酶(MPO)、丙二醛(MDA)。结果:7d组组织学损伤评分、IAI评分分别为(4.8±0.8)、(3.0±0.5),明显低于3d组(6.9±0.7)、(5.1±0.6)(P<0.05);7d组MDA、MPO及NFκ-B表达的阳性细胞百分率、平均光密度值为[(3.8±0.5)、(2.2±0.4)、(21.3±3.5)%、(51.1±2.9)],均少于3d组[(5.1±0.8)、(3.4±0.5)、(52.1±2.4)%、(65.4±3.4)](P<0.05)。结论:NBD多肽对于溃疡性结肠炎大鼠模型有较好的治疗作用,随着时间的延长,疗效逐渐增强,其作用与其抑制NFκ-B表达有关。OBJECTIVE To observe the time-activity-curve of the therapeutic effect of micromolecule polypeptide combining with NEMO-binding domain on experimental ulcerative colitis rat. METItODS Sixty four SD rats were randomly divided into treated and control group, then every group divided into eight small groups. Ulcerative colitis rat model was induced by enteroelysis with trinitro- benzene-sulfonic acid（TNBS）, micromolecule polypeptide combining with NEMO-binding domain were administered by intraperitoneal injection in treated group, and Ejusd dose＇s liquor natrii chloridi isotonicus were administered likely in control group. IAI score were evaluated assay. Then the rats were killed in 3 days, 7 days after model was made by groups for the observation of the colonic pathologic changes by naked eye and for the estimation of the damage scores of colon mucosa. Finally, the colon tissue was fixed to make pathological section and the damage score of tissue was observed under microscope. The damaged colon tissue＇s pathological sections were taken to test expression of NF-κB by immunizing histoehemistry. Then the value of MDA,MPO in supernatant of samples＇ damaged colon tissue＇s were tested according to the instruction of the corresponding kit. RESULTS The 7d group＇ s damage scores of tissue, IAI score are 4. 8 ± 0. 8,3. 0 ± 0. 5, and they all are lower than that of the 7d group（6. 9 ± 1. 1 ）, （5. 1 ± 0. 6） （P〈0. 05）. And the value of the 7d group＇s MPO,MDA,percentage of positive cell and mean optic density of NF-κB are （3. 8 ± 0. 5）, （2. 2 ± 0. 4）, （21.3 ± 3. 5） %, （51.1 ± 2. 9）, and they are lower than that of the 3d group（5.1 ± 0. 8）, （3.4 ± 0. 5）, （52. 1 ± 2. 4） %, （65.4 ± 3. 4） （P〈0. 05）. CONCLUSION Micromolecule polypeptide combining with NEMO-binding domain has protective effect against rat ulcerative colitis, and its mechanism of action relates with the inhibition of nuclear factor κB.

关 键 词：NEMO结合的小分子多肽 溃疡性结肠炎 动物模型 NF-ΚB 免疫组化 

分 类 号：R285.5[医药卫生—中药学]