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比较分析昆明小鼠在链脲佐菌素和天然食物诱导的 2 型糖尿病中的肝脏特异性转录组谱。

Comparatively analyzing the liver-specific transcriptomic profiles in Kunming mice afflicted with streptozotocin- and natural food-induced type 2 diabetes mellitus.

机构信息

Institute of Laboratory Animal Research, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China.

College of Animal Science & Technology, Guangxi University, Nanning, 530004, China.

出版信息

Mol Biol Rep. 2022 Feb;49(2):1369-1377. doi: 10.1007/s11033-021-06970-1. Epub 2021 Nov 30.

DOI:10.1007/s11033-021-06970-1
PMID:34846649
Abstract

BACKGROUND

Streptozotocin is a classic drug used to induce diabetes in animal models.

OBJECTIVE

The aim of this study is to investigate the liver transcriptome of Kunming mice with diabetes induced by either streptozotocin (STZ) or Non-STZ.

METHODS

Forty male mice were randomly assigned into four groups: Control (Ctr, standard diet), mHH (high fat and high carbohydrate diet), mHS (high fat and high carbohydrate diet for 4 weeks followed by 60 mg/kg STZ for 3 consecutive days) and mSH (60 mg/kg STZ for 3 consecutive days followed by a high fat and high carbohydrate diet for 12 weeks). All mice injected with STZ were identified as diabetic despite the sequential feeding of high fat and high carbohydrate diets.

RESULTS

Only 7 of 13 mice in the mHH group met the diagnostic criteria for diabetes. The asting blood glucose (FBG) of the mHH, mHS, mSH and Ctrl groups was 13.27 ± 1.14, 15.01 ± 2.59, 15.95 ± 4.38 and 6.28 ± 0.33 mmol/L at the 12th week, respectively. Compared with the mHH group, transcription was elevated in 85 genes in the livers of mHS mice, while 21 genes were downregulated and 97 genes were upregulated in the mSH group while 35 genes were decreased. A total of 43 co-expressed genes were identified in the mHS vs mHH and mSH vs mHH groups. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses showed that two corporate GO terms and two KEGG pathways were significantly annotated in the STZ-treated groups. Both the GO term and pathway were related to the metabolism mediated by p53.

CONCLUSION

A high fat and high carbohydrate diet combined with a low dose of STZ can effectively induce diabetes in Kunming mice despite the abnormal expressions of genes in the liver. The differentially expressed genes were related to metabolism mediated by p53.

摘要

背景

链脲佐菌素是一种经典的用于诱导动物模型糖尿病的药物。

目的

本研究旨在探讨昆明小鼠经链脲佐菌素(STZ)或非 STZ 诱导糖尿病后的肝转录组。

方法

将 40 只雄性小鼠随机分为 4 组:对照组(Ctr,标准饮食)、mHH(高脂肪高碳水化合物饮食)、mHS(高脂肪高碳水化合物饮食 4 周后连续 3 天给予 60mg/kg STZ)和 mSH(连续 3 天给予 60mg/kg STZ 后给予高脂肪高碳水化合物饮食 12 周)。尽管连续给予高脂肪高碳水化合物饮食,但所有注射 STZ 的小鼠均被鉴定为糖尿病。mHH、mHS、mSH 和 Ctrl 组的空腹血糖(FBG)在第 12 周时分别为 13.27±1.14mmol/L、15.01±2.59mmol/L、15.95±4.38mmol/L和 6.28±0.33mmol/L。与 mHH 组相比,mHS 组小鼠肝脏中 85 个基因的转录水平升高,而 mSH 组中 21 个基因下调,97 个基因上调,同时 35 个基因下调。在 mHS 与 mHH 组和 mSH 与 mHH 组中总共鉴定出 43 个共表达基因。GO(基因本体论)和 KEGG(京都基因与基因组百科全书)分析表明,在 STZ 处理组中,有两个共同的 GO 术语和两个 KEGG 途径被显著注释。GO 术语和途径均与 p53 介导的代谢有关。

结论

高脂肪高碳水化合物饮食联合低剂量 STZ 可有效诱导昆明小鼠糖尿病,尽管肝脏中基因表达异常。差异表达基因与 p53 介导的代谢有关。

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Endoplasmic reticulum stress and renal lesion in mice with combination of high-fat diet and streptozotocin-induced diabetes.
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Acta Cir Bras. 2016 Mar;31(3):150-5. doi: 10.1590/S0102-865020160030000001.
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