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[胰高血糖素样肽-1受体激动剂对肥胖小鼠肝脏脂肪变性的初步研究]

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

作者信息

Wang Xia, He He, Liang Li-Bo, Zhang Mei, Li She-Yu, Li Shuang-Qing, An Zhen-Mei, Huang Heng-Jian

机构信息

Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.

Department of General Practice, West China Hospital, Sichuan University, Chengdu 610041, China.

出版信息

Sichuan Da Xue Xue Bao Yi Xue Ban. 2017 Jan;48(1):28-32.

Abstract

OBJECTIVES

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 ( <0.05). The serum alanine aminotransferase (ALT) level of NG group was higher than that of H, L, M, and NS groups ( <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, and amylase had no significant differences between groups (>0.05). Hepatic steatosis score was reduced by diet intervention or drug treatment.

CONCLUSIONS

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.

摘要

目的

研究胰高血糖素样肽-1(GLP-1)受体激动剂艾塞那肽对肥胖小鼠肝功能和脂肪变性的影响。

方法

将8周龄雄性C57BL/6J小鼠分为高脂饮食组(用于构建肥胖模型)和正常饮食组。12周后,将高脂饮食组小鼠随机分为高剂量艾塞那肽组[H组,腹腔注射0.02μg/(g·d),高脂饮食]、低剂量艾塞那肽组[L组,腹腔注射0.01μg/(g·d),高脂饮食]、生理盐水组(NS组,腹腔注射生理盐水,高脂饮食)、饮食对照组(D组,改为正常饮食)和高脂对照组(M组,高脂饮食),分别进行为期4周的治疗。检测小鼠体重和血清生化指标。对肝组织进行HE染色,并测量脂肪变性评分。

结果

经过4周治疗后,H组体重减轻比L组和D组更多(P<0.05)。NG组血清丙氨酸氨基转移酶(ALT)水平高于H、L、M和NS组(P<0.05)。通过饮食干预或药物治疗,血清胆固醇和甘油三酯降至正常水平。高剂量艾塞那肽治疗有增加血清尿酸水平的风险。各组间血清天冬氨酸氨基转移酶(AST)、葡萄糖、稳态模型评估胰岛素抵抗(HOMA-IR)、脂肪酶和淀粉酶水平无显著差异(P>0.05)。饮食干预或药物治疗可降低肝脏脂肪变性评分。

结论

高剂量艾塞那肽治疗可有效减轻肥胖小鼠体重,但在改善血脂和肝脏脂肪变性方面与饮食干预相比差异不大。

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