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一种胰高血糖素样肽-1类似物，利拉鲁肽，通过微小RNA改善内皮功能障碍以抑制大鼠细胞凋亡。

A glucagon-like peptide-1 analog, liraglutide, ameliorates endothelial dysfunction through miRNAs to inhibit apoptosis in rats.

作者信息

Zhang Qian, Xiao Xinhua, Zheng Jia, Li Ming

机构信息

Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

出版信息

PeerJ. 2019 Mar 6;7:e6567. doi: 10.7717/peerj.6567. eCollection 2019.

DOI:10.7717/peerj.6567
PMID:30863684
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6408912/
Abstract

BACKGROUND AND AIMS

Many studies have revealed that glucagon-like peptide-1 has vasoprotective effects. In this study, we investigated whether liraglutide suppressed endothelial dysfunction and explored the mechanism involved.

METHODS

Experimental diabetes was induced through combined high-fat diet administration and intraperitoneal streptozotocin injections. Rats were randomly divided into the following four groups: control, diabetes, diabetes + a low liraglutide dose (0.2 mg/kg/d), and diabetes + a high liraglutide dose (0.4 mg/kg/d). Endothelial function and metabolic parameters were measured after 8 weeks of treatment. miRNA arrays were analyzed to identify the differentially expressed miRNAs.

RESULTS

We found that liraglutide significantly improved aortic endothelial function in diabetic rats. Liraglutide inhibited miR-93-5p, miR-181a-5p and miR-34a-5p expression, and activated miR-26a-5p expression. miRNA mimic transfection experiments indicated negative relationships between miR-93-5p, miR-181a-5p, miR-34a-5p, and miR-26a-5p and Sirt1, Creb, Bcl-2, and Pten expression, respectively. Moreover, liraglutide increased Sirt1, Creb, and Bcl-2 expression levels and reduced Pten expression level.

CONCLUSION

Our results demonstrate the role of key miRNAs in the liraglutide-mediated regulation of endothelial cell function in diabetic rats.

摘要

背景与目的

许多研究表明胰高血糖素样肽-1具有血管保护作用。在本研究中，我们调查了利拉鲁肽是否能抑制内皮功能障碍并探索其相关机制。

方法

通过联合高脂饮食和腹腔注射链脲佐菌素诱导实验性糖尿病。大鼠被随机分为以下四组：对照组、糖尿病组、糖尿病+低剂量利拉鲁肽组（0.2毫克/千克/天）和糖尿病+高剂量利拉鲁肽组（0.4毫克/千克/天）。治疗8周后测量内皮功能和代谢参数。分析miRNA阵列以鉴定差异表达的miRNA。

结果

我们发现利拉鲁肽显著改善了糖尿病大鼠的主动脉内皮功能。利拉鲁肽抑制了miR-93-5p、miR-181a-5p和miR-34a-5p的表达，并激活了miR-26a-5p的表达。miRNA模拟物转染实验表明，miR-93-5p、miR-181a-5p、miR-34a-5p与miR-26a-5p分别与Sirt1、Creb、Bcl-2和Pten的表达呈负相关。此外，利拉鲁肽增加了Sirt1、Creb和Bcl-2的表达水平，并降低了Pten的表达水平。

结论

我们的结果证明了关键miRNA在利拉鲁肽介导的糖尿病大鼠内皮细胞功能调节中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/213e/6408912/d06364c3d2c7/peerj-07-6567-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/213e/6408912/37dfb44cddce/peerj-07-6567-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/213e/6408912/0bbe2a717bd7/peerj-07-6567-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/213e/6408912/49d1230bef43/peerj-07-6567-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/213e/6408912/183855ec46c6/peerj-07-6567-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/213e/6408912/461ab7eeac34/peerj-07-6567-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/213e/6408912/bdb28503fc76/peerj-07-6567-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/213e/6408912/d06364c3d2c7/peerj-07-6567-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/213e/6408912/37dfb44cddce/peerj-07-6567-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/213e/6408912/0bbe2a717bd7/peerj-07-6567-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/213e/6408912/49d1230bef43/peerj-07-6567-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/213e/6408912/183855ec46c6/peerj-07-6567-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/213e/6408912/461ab7eeac34/peerj-07-6567-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/213e/6408912/bdb28503fc76/peerj-07-6567-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/213e/6408912/d06364c3d2c7/peerj-07-6567-g007.jpg

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