替度鲁肽对大鼠非酒精性脂肪性肝病的治疗作用  

Therapeutic effect of teduglutide on non-alcoholic fatty liver disease in rats

作　　者：胡银霞[1] 李兰[2] 袁瑜[2] 吴礼浩[2] 何兴祥[2] 

机构地区：[1]广东药学院临床医学院,广东省广州市510006 [2]广东药学院附属第一医院消化内科,广东省广州市510080

出　　处：《世界华人消化杂志》2016年第7期1009-1016,共8页World Chinese Journal of Digestology

基　　金：广东省医学科研基金资助项目;No.A2014363~~

摘　　要：目的:探讨GLP-2类似物替度鲁肽治疗大鼠非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的作用.方法:30只SD大鼠随机分为正常饮食组和高脂饮食组,至第12周末时两组分别取6只大鼠判断NAFLD造模成功与否.第13周起,以剩余正常饮食组大鼠为对照(n=6),高脂饮食组随机分为NAFLD组(n=6)和GLP-2组(n=6),其中GLP-2组注射替度鲁肽液,对照组和NAFLD组注射生理盐水,7 d后眼眶取血并处死取材,检测NAFLD相关生化指标和病理观察.结果:NAFLD模型成功构建,高脂饮食组肝脏匀浆的总甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)及肝脏活动度积分(NAFLD activity score,NAS)均高于正常饮食组(P<0.05);且高脂饮食组十二指肠肠道黏膜上皮细胞排列疏松、间隙变大,黏膜Claudin-2蛋白表达增多(P<0.05).给药G L P-2后,肝脏匀浆的T G、T C及肝脏N A S均低于NAFLD组(P<0.05);且改善了肠道黏膜上皮细胞的排列,减小了细胞间隙和黏膜Claudin-2蛋白的表达(P<0.05).结论:NAFLD发病可导致肠道黏膜细胞间隙增大,Claudin-2蛋白表达升高,替度鲁肽可能通过降低NAFLD大鼠肠道黏膜Claudin-2蛋白的表达,从而改善NAFLD的肝脏病变.AIM：To assess the therapeutic effect of glucagon-like peptide（GLP-2） analogue teduglutide on non-alcoholic fatty liver disease（NAFLD） in rats.METHODS：Thirty SD rats were randomized into a normal diet group and a high-fat diet group.After feeding for 12 weeks,six rats were respectively selected from the two groups to determine whether the NAFLD model was successfully established.From the 13 th week,the rest rats in the normal diet group served as controls（n = 6）,and the rest rats of the highfat diet group were randomized into a NAFLD group（n.= 6） and a GLP-2 group（ft = 6）.The rats in the GLP-2 group were injected with teduglutide and the other two groups were injected with normal saline for 7 days.Then blood samples were collected from the ocular veniplex and rats were sacrificed.NAFLD related biochemical indicators were determined and pathological results were observed.RESULTS：The NAFLD model was successfully established.Compared to the normal group,triglyceride（TG） and total cholesterol（TC） levels in liver homogenate and NAFLD activity score（NAS） were significantly higher in the high-fat diet group（P 0.05）.Moreover,duodenal mucosal epithelial cells were loosely arranged,and intercellular space and Claudin-2 protein expression were increased（P 0.05）.After treatment with GLP-2,TG and TC levels in liver homogenate and liver NAS were significantly lower than those of the NAFLD group（P 0.05）.Accordingly,the arrangement of intestinal epithelial cells was improved,and intercellular space and Claudin-2 protein expression were decreased（P 0.05）.CONCLUSION：NAFLD can cause the loose of intestinal mucosal cells and the increase of Claudin-2 protein expression.Teduglutide might exert its therapeutic effect on NAFLD by decreasing the expression of Claudin-2 protein.

关 键 词：非酒精性脂肪性肝病 Claudin-2蛋白 替度鲁肽 

分 类 号：R575.5[医药卫生—消化系统]