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六个月高脂肪饮食和果糖-葡萄糖饮料联合应用于非酒精性脂肪肝疾病小鼠模型的部分验证。

Partial validation of a six-month high-fat diet and fructose-glucose drink combination as a mouse model of nonalcoholic fatty liver disease.

机构信息

First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece.

出版信息

Endocrine. 2024 Aug;85(2):704-716. doi: 10.1007/s12020-024-03769-5. Epub 2024 Mar 20.

Abstract

PURPOSE

The need to investigate the pathogenesis and treatment of nonalcoholic fatty liver disease (NAFLD) has led to the development of multiple mouse models. The aim of this study was to validate a fast food diet (FFD) mouse model that is introduced as being close to the human disease.

METHODS

Eight to nine weeks old male and female C57BL/6 J mice were randomly allocated to a FFD group or to a chow diet (CD) group. Every four weeks, mice were weighed, and blood samples were collected for the measurement of glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TGs) and total cholesterol. After 25 weeks, mice were sacrificed, and liver tissue was histologically evaluated.

RESULTS

FFD mice gained more weight (p = 0.049) and presented a higher liver-to-body weight ratio (p < 0.001) compared to CD mice. FFD group presented with greater steatosis, hepatocellular ballooning and NAFLD activity score (NAS), whereas lobular inflammation and fibrosis were not significantly different compared to CD. When stratified by sex, NAS was different between FFD and CD groups in both male and female mice. Group by time interaction was significant for weight, ALT and cholesterol, but not for glucose, AST and TGs.

CONCLUSION

FFD mice presented with morphologic and biochemical features of NAFLD and with greater hepatic steatosis, hepatocellular ballooning and NAS, but not lobular inflammation and fibrosis, compared to CD mice. These results only partly validate the FFD mouse model for NAFLD, at least for a 6-month feeding period.

摘要

目的

为了研究非酒精性脂肪性肝病(NAFLD)的发病机制和治疗方法,已经开发出多种小鼠模型。本研究旨在验证一种快餐饮食(FFD)小鼠模型,该模型被认为与人类疾病更为接近。

方法

将 8 至 9 周龄雄性和雌性 C57BL/6J 小鼠随机分配到 FFD 组或标准饮食(CD)组。每四周测量一次体重,并采集血样,以测量血糖、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、甘油三酯(TGs)和总胆固醇。25 周后,处死小鼠,对肝组织进行组织学评估。

结果

与 CD 组相比,FFD 组小鼠体重增加更多(p=0.049),肝重与体重比更高(p<0.001)。FFD 组小鼠表现出更严重的脂肪变性、肝细胞气球样变和 NAFLD 活动评分(NAS),而肝小叶炎症和纤维化程度与 CD 组无显著差异。按性别分层时,FFD 组和 CD 组的 NAS 在雄性和雌性小鼠中均有差异。体重、ALT 和胆固醇的组间时间交互作用有统计学意义,但血糖、AST 和 TGs 无统计学意义。

结论

与 CD 组相比,FFD 组小鼠表现出 NAFLD 的形态和生化特征,且肝脂肪变性、肝细胞气球样变和 NAS 更严重,但肝小叶炎症和纤维化程度无差异。至少在 6 个月的喂养期间,该 FFD 小鼠模型仅部分验证了 NAFLD。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae89/11291610/35998cfed44e/12020_2024_3769_Fig1_HTML.jpg

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