胰高血糖素样肽-1类似物对小鼠实验性结肠炎的治疗作用  

Therapeutic effect of glucagon-like-peptide-1 analog on dextran sulfate sodium induced experimental colitis in mice

作　　者：刘红霞[1] 李晓雯[1] 罗登[1] 林紫薇[1] 慕开达[1] 王琛[1] 贾伟平[1] 

机构地区：[1]上海交通大学附属第六人民医院内分泌与代谢科,上海市糖尿病研究所上海市糖尿病重点实验室,上海200233

出　　处：《上海医学》2014年第9期770-773,I0003,共5页Shanghai Medical Journal

基　　金：上海市科技创新重点项目资助(11140900900)

摘　　要：目的明确胰高血糖素样肽(GLP)-1类似物对小鼠实验性结肠炎是否具有治疗作用,并探讨其可能的作用机制。方法将C57BL/6J小鼠随机分入正常对照组(饮用蒸馏水)、结肠炎模型组(给予体积分数为0.02的葡聚糖硫酸钠溶液,连续自由饮用7d诱导结肠炎模型)和利拉鲁肽治疗组(从造模前3d开始至造模结束,腹腔注射由诺和诺德公司提供的利拉鲁肽2次/d,1mg/kg,持续给药10d),每组7只。通过监测小鼠粪便性状和粪隐血获得临床模拟评分,通过评估结肠病理切片的组织损伤和炎性细胞浸润获得组织评分,采用实时定量聚合酶链反应检测结肠组织细胞因子的表达水平。结果利拉鲁肽治疗组小鼠的临床模拟评分为(2.86±0.32)分,显著低于结肠炎模型组的(3.79±0.18)分(P<0.05);结肠长度为(4.80±0.08)cm,显著长于结肠炎模型组的(4.46±0.12)cm(P<0.05);组织评分为(2.33±0.21)分,显著低于结肠炎模型组的(5.43±0.57)分(P<0.01)。结肠炎模型组小鼠白细胞介素(IL)-1β的相对表达量是正常对照组的(43.53±16.75)倍(P<0.05),但两组间肿瘤坏死因子(TNF)-α、IL-10和转化生长因子(TGF)-β的相对表达量的差异无统计学意义(P值均>0.05)。利拉鲁肽治疗组与结肠炎模型组小鼠间TNF-α、IL-1β、IL-10的差异均无统计学意义(P值均>0.05),但利拉鲁肽治疗组小鼠TGF-β的相对表达量是结肠炎模型组的(2.74±0.98)倍(P=0.07)。结论 GLP-1类似物可减轻葡聚糖硫酸钠诱导的小鼠实验性结肠炎,此作用可能与调节细胞因子有关。Objective To investigate the effect of glucagon-like-peptide-1 （GLP-1） analog on experimental colitis in mice and the possible mechanism. Methods C57BL/6J mice were randomly divide into three groups （n = 7 in each）., normal control group, dextran sulfate sodium （DSS） group and treatment （liraglutide） group. Colitis was induced by feeding with 2% （w/v） DSS in the distilled drinking water for 7 days. Mice were treated with a long-acting GLP-1 analog, liraglutide, injected twice daily （1 mg/kg） 3 days before the administration of DSS for 10 days. Clinical score was determined by quantifying stool consistency and hemoccult positive rate. Tissue score was determined by evaluating tissue lesion and inflammatory cell infiltration under pathological section. Real-time polymerase chain reaction （PCR） was conducted to analyze cytokine expression in colon tissue. Results Both clinical and tissue scores of liraglutide group were significantly lower than those in DSS group （clinical score.- 2.86±0.32 vs. 3.79±0.18, tissue score： 2.33±0.21 vs. 5.43±0.57, both P〈0.05）. The length of colon in liraglutide group was significantly longer than that in DSS group （4.80 ± 0. 081 cm vs. [-4.46± 0. 121 cm, P〈0.05）. The expression of interleukin 16 （IL-1β） in DSS group was （43.53± 16.75） folds as compared with normal control group （P〈0.05）, but there were no significant differences in tumor necrosis factor α （TNF-α）, interleukin 10 （IL-10） or transforming growth factor （TGF-α） between the two groups （all P〈 0.05）. There were no significant differences in TNF-α, IL-113, or IL-10 between liraglutide group and DSS group （all P〉0.05）, but the expression of TGF-αwas （2.74 ± 0.98） folds as compared with DSS group （ P = 0.07）. Conclusion GLP-1 analog can reduce DSS-induced experimental colitis in mice, which may react through meditating the expression of cytokines.

关 键 词：胰高血糖素样肽-1 结肠炎 细胞因子 

分 类 号：R574.62[医药卫生—消化系统]