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枸杞多糖对妊娠期糖尿病小鼠影响的外泌体微小RNA表达谱分析

Exosomal MicroRNA Expression Profiling Analysis of the Effects of Lycium Barbarum Polysaccharide on Gestational Diabetes Mellitus Mice.

作者信息

Xiao Ya, Chen Weihao, Chen Ruixue, Luo Anling, Chen Dayi, Liang Qiuer, Liu Tianhao, Chen Xudong, Tan Wei

机构信息

School of Traditional Chinese Medicine, Jinan University, Guangzhou, China.

The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

出版信息

Evid Based Complement Alternat Med. 2020 Jul 30;2020:2953502. doi: 10.1155/2020/2953502. eCollection 2020.

DOI:10.1155/2020/2953502
PMID:32802120
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7414337/
Abstract

OBJECTIVE

Gestational diabetes mellitus (GDM) is a pathological condition, affecting an increasing number of pregnant women worldwide. Safe and effective treatment for GDM is very important for the public health. In this study, we utilized a high-fat diet-induced GDM model to evaluate the effects of LBP on GDM and examined the changes of exosomal microRNA expression profiling to decipher the potential underlying mechanism of LBP.

METHODS

Female C57BL/6J mice were fed a control diet, HFD, or 150 mg/kg LBP-supplemented HFD for 6 weeks before conception and throughout gestation. Oral glucose tolerance test and plasma lipid levels were determined, and liver histopathology was assessed. Sequencing was used to define the microRNA expression profiling of plasma exosomes in the three groups of mice, and protein expression levels of the candidate target genes were analyzed.

RESULTS

LBP significantly relieved glucose intolerance, abnormal plasma lipid levels, and pathomorphological changes of liver histopathology in HFD-induced GDM mice. Moreover, we found that this effect of LBP was mediated by downregulation of the increase of 6 miRNAs (miR-93-3p, miR-188-5p, miR-466k, miR-1188-5p, miR-7001-3p, and miR-7115-5p) and reversing the increase of the protein expression of CPT1A, which is the target gene of miR-188-5p.

CONCLUSIONS

Our findings provide novel insights into the biological activities of LBP in the treatment of GDM.

摘要

目的

妊娠期糖尿病(GDM)是一种病理状态,在全球影响着越来越多的孕妇。GDM的安全有效治疗对公众健康非常重要。在本研究中,我们利用高脂饮食诱导的GDM模型来评估枸杞多糖(LBP)对GDM的影响,并检测外泌体微小RNA表达谱的变化,以阐明LBP潜在的作用机制。

方法

雌性C57BL/6J小鼠在受孕前6周及整个妊娠期分别喂食对照饮食、高脂饮食(HFD)或添加150mg/kg LBP的HFD。测定口服葡萄糖耐量试验和血浆脂质水平,并评估肝脏组织病理学。采用测序法确定三组小鼠血浆外泌体的微小RNA表达谱,并分析候选靶基因的蛋白表达水平。

结果

LBP显著缓解了HFD诱导的GDM小鼠的葡萄糖不耐受、异常血浆脂质水平及肝脏组织病理学的病理形态学变化。此外,我们发现LBP的这种作用是通过下调6种微小RNA(miR-93-3p、miR-188-5p、miR-466k、miR-1188-5p、miR-7001-3p和miR-7115-5p)的增加,并逆转miR-188-5p靶基因CPT1A蛋白表达的增加来介导的。

结论

我们的研究结果为LBP治疗GDM的生物学活性提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6138/7414337/4fc35d9fbeb7/ECAM2020-2953502.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6138/7414337/b8d1b14ad6b5/ECAM2020-2953502.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6138/7414337/a7c1fc850170/ECAM2020-2953502.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6138/7414337/cee0a2f4c5a3/ECAM2020-2953502.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6138/7414337/94073fc625a9/ECAM2020-2953502.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6138/7414337/530995b97a8a/ECAM2020-2953502.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6138/7414337/536874762193/ECAM2020-2953502.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6138/7414337/4fc35d9fbeb7/ECAM2020-2953502.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6138/7414337/b8d1b14ad6b5/ECAM2020-2953502.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6138/7414337/a7c1fc850170/ECAM2020-2953502.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6138/7414337/cee0a2f4c5a3/ECAM2020-2953502.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6138/7414337/94073fc625a9/ECAM2020-2953502.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6138/7414337/530995b97a8a/ECAM2020-2953502.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6138/7414337/536874762193/ECAM2020-2953502.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6138/7414337/4fc35d9fbeb7/ECAM2020-2953502.007.jpg

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