GLP-1受体激动剂对肥胖小鼠肝脏脂肪变性的影响  

The Preliminary Investigation of GLP-1 Receptor Agonist on Liver Steatosis in Obese Mice

作　　者：王霞[1] 何訸[1] 梁利波[2] 张玫[1] 李舍予[3] 李双庆[2] 安振梅[3] 黄亨建[1] 

机构地区：[1]四川大学华西医院实验医学科,成都610041 [2]四川大学华西医院全科医学科,成都610041 [3]四川大学华西医院内分泌代谢科,成都610041

出　　处：《四川大学学报（医学版）》2017年第1期28-32,40,共6页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金青年项目(No.81501800和No.81400811)资助

摘　　要：目的探讨胰高血糖素样肽1(GLP-1)受体激动剂艾塞那肽对肥胖小鼠肝脏脂肪变性及肝功能的影响。方法将8周龄雄性C57BL/6J小鼠随机分为普通饲料组(NG)和高脂饲料组(HG)喂养12周,HG组肥胖模型建模成功后再随机分为高剂量艾塞那肽组〔H组,腹腔注射0.02μg/(g·d),高脂饲料喂养〕、低剂量艾塞那肽组〔L组,腹腔注射0.01μg/(g·d),高脂饲料喂养〕、生理盐水对照组(NS组,腹腔注射等量生理盐水,高脂饲料喂养)、饮食干预组(D组,更换为普通饲料喂养)、高脂对照组(M组,继续高脂饲料喂养)进行干预,干预4周;NG组继续喂养4周。干预4周后分别测量各组小鼠的血清生化指标,包括血脂、肝功能、血糖(Glu)、尿酸(SUA)、胰岛素(INS),计算胰岛素抵抗指数(HOMA-IR),观察体质量变化情况,并取肝组织行HE染色,评估脂肪变性程度。结果治疗4周后,NS组、M组小鼠体质量均较治疗前增加(P<0.001):H、L、D组小鼠体质量均较治疗前降低,且H组小鼠体质量降低较L组及D组明显(P<0.05)。H组、L组、M组、NS组丙氨酸氨基转移酶(ALT)水平低于NG组(P<0.05)。饮食治疗和药物治疗都可降低三酰甘油(TG)和总胆固醇(TC)至正常水平〔NS组高于NG组(P<0.05),NG组与H组、L组、D组的差异无统计学意义(P>0.05)〕,但H组、L组和D组在TC、TG水平的组间差异无统计学意义(P>0.05)。高剂量药物治疗存在SUA水平升高的风险〔H组SUA水平高于其余各组(P<0.05)〕。门冬氨酸氨基转移酶(AST)、Gly、HOMA-IR、脂肪酶(LIP)、淀粉酶(AMY)各组间差异无统计学意义(P>0.05)。饮食治疗和药物治疗均可改善肝组织的脂肪变性〔NS组脂肪变性评分高于NG组(P<0.05),H、L、D组脂肪变性评分与NG组差异无统计学意义(P>0.05)〕。结论高剂量GLP-1受体激动剂能有效降低肥胖小鼠体质量,但在改善血脂和肝细胞脂肪变性方面与饮食干预差别不大。Objective To investigate the effects of glueagon-like peptide-1 （GLP-1） receptor agonist, exenatide,on liver function and steatosis in obese mice. Methods Male c57BL/6J mice （8 weeks old） were divided into high-fat-diet group （for obesity model construction） and chow diet group. 12 weeks later, mice of high-fat diet group were randomly divided into high-dose exenatide group [H group, intraperitoneal injection 0.02 μg/（g · d）, high fat-diet], low dose exenatide group [L group, intraperitoneal injection 0.01 μg/（g · d）, high fat-diet], saline group （NS group, intraperitoneal injection of saline, high-fat-diet）, diet control group （D group, shifted to chow diet） and high-fat control group （M group, high-fat-diet） for 4 week treatments ,respectively. The body mass and serum biochemical indicators of were detected. I.iver tissues were stained with HE, and steatosis score was measured. Results After 4-week treatments, H group showed more body mass loss than L group and D group （P〈0.05）. The serum alanine aminotransferase （ALT） level of NG group was higher than that of H, i.,M, and NS groups （P〈0. 05）. Serum cholesterol and triglyceride declined to normal levels by diet intervention or drug treatment. High-dose exenatide treatment ran a risk of increasing serum uric acid level. The serum levels of aspartate aminotransferase （AST）, glucose, homeostasis model assessment-insulin resistance （HOMAqR）, lipase,and amylase had no significant differences between groups （P〉0. 05）. Hepatic steatosis score was reduced by diet intervention or drug treatment. Coneluslon High-dose exenatide treatment can effectively reduce body mass of obese mice, but it has little difference when compared with dietary intervention in improving blood fat and liver steatosis.

关 键 词：肥胖 GLP-1受体激动剂 肝脏脂肪变性 

分 类 号：R589.2[医药卫生—内分泌]