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GLP-1受体激动剂对肥胖小鼠肝脏脂肪变性的影响

  • 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0.02 μg/(g·d),高脂饲料喂养〕、低剂量艾塞那肽组〔L组,腹腔注射0.01 μg/(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。

     

    Abstract: Objective To investigate the effects of glucagon-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. Liver 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, L,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 (HOMA-IR), lipase,

     

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