CCR5第一、二胞外环特异性结合的拮抗短肽对TNBS诱导SD大鼠结肠炎的治疗作用  

Effects of antagonistic peptides binding specifically with first and second extracellular loops of CCR5 on colitis rats induced by TNBS

作　　者：胡梅[1] 宋杨达 刘思雪[1] 宋铱航 沈溪明[2] 黄花荣[3] 钟英强[1] 

机构地区：[1]中山大学孙逸仙纪念医院消化内科,广东广州510120 [2]中山大学孙逸仙纪念医院病理科,广东广州510120 [3]中山大学孙逸仙纪念医院儿科,广东广州510120

出　　处：《中国病理生理杂志》2017年第5期902-907,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81370499);广东省自然科学基金资助项目(No.2014A030313020;No.2016A03031343)

摘　　要：目的:研究C-C趋化因子受体5(CCR5)膜外第一、二胞外环(ECL1和ECL2)特异性结合的拮抗短肽对三硝基苯磺酸(TNBS)诱导的结肠炎模型大鼠的治疗作用与机制。方法:采用100 mg/kg TNBS诱导结肠炎SD大鼠模型;用不同剂量的2条拮抗短肽(ECL1:25、35和45 mg/kg;ECL2:15、25和35 mg/kg)分别作用于模型大鼠,观察其对大鼠疾病活动指数(DAI)、结肠大体损伤指数(CMDI)和组织病理学改变的影响,采用real-time PCR和Western blot法分别检测结肠组织TNF-α和COX-2的mRNA与蛋白表达水平。结果:与模型组相比,有效剂量的ECL2拮抗短肽HY治疗组大鼠疾病活动程度、肠道溃疡及病理组织学损伤均有明显减轻,各评分指数差异具有统计学意义(P<0.05);TNF-α和COX-2的蛋白和mRNA表达水平均明显下降(P<0.05)。ECL1拮抗短肽GH作用的大鼠结肠炎症状评分及TNF-α和COX-2炎症因子表达无明显改变。结论:ECL2拮抗短肽可能通过下调结肠黏膜TNF-α和COX-2的表达来缓解TNBS诱导的SD大鼠结肠炎,而ECL1拮抗短肽的作用不明显。AIM： To study the effects of antagonistic peptides binding specifically with the first and second extracellular loops （ECL1 and ECL2） of C-C chemokine receptor 5 （CCR5） on the colitis rats induced by trinitrobenzenesulfonic acid （TNBS） and the mechanisms.METHODS： The colitis model of SD rats was induced by TNBS （100 mg/kg）. The effects of 2 antagonistic peptides at different doses （ECL1：25, 35 and 45 mg/kg; ECL2：15, 25 and 35 mg/kg） on the model rats including the changes of disease activity index （DAI）, colon macroscopic damage index （CMDI） and histological grading were observed. The mRNA and protein expression levels of TNF-α and COX-2 in the colonic mucosa were detected by real-time PCR and Western blot, respectively.RESULTS： Compared with model group, the changes of DAI, CMDI and histopathological injury of the rats treated with ECL2 antagonistic peptide HY at an appropriate dose were significantly reduced （P〈0.05）, and the protein and mRNA expression levels of TNF-α and COX-2 were significantly decreased （P〈0.05）. However, the effects of ECL1 antagonistic peptide GH on all scores and the expression levels of TNF-α and COX-2 were not obvious.CONCLUSION： ECL2 antagonistic peptide HY relieves TNBS-induced colitis in SD rats via down-regulating the expressions of TNF-α and COX-2 in the colonic mucosa, while the effect of ECL1 antagonist peptide GH was not obvious.

关 键 词：C-C趋化因子受体5 拮抗肽 炎症性肠病 

分 类 号：R363[医药卫生—病理学] R965.2[医药卫生—基础医学]