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鸢尾素通过AMPK途径减轻糖尿病小鼠的心肌缺血/再灌注损伤并改善线粒体功能。

Irisin Attenuates Myocardial Ischemia/Reperfusion Injury and Improves Mitochondrial Function Through AMPK Pathway in Diabetic Mice.

作者信息

Xin Chao, Zhang Zheng, Gao Guojie, Ding Liping, Yang Chao, Wang Chengzhu, Liu Yanjun, Guo Yufei, Yang Xueqing, Zhang Lijuan, Zhang Lina, Liu Yi, Jin Zhitao, Tao Ling

机构信息

Department of Cardiology, PLA Rocket Force Characteristic Medical Center, Beijing, China.

Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China.

出版信息

Front Pharmacol. 2020 Sep 11;11:565160. doi: 10.3389/fphar.2020.565160. eCollection 2020.

Abstract

AIMS

Several recent reports have shown irisin protects the heart against ischemia/reperfusion injury. However, the effect of irisin on I/R injury in diabetic mice has not been described. The present study was designed to investigate the role of irisin in myocardial ischemia-reperfusion (MI/R) injury in diabetic mice.

METHODS

A mouse model of diabetes was established by feeding wild type or gene-manipulated adult male mice with a high-fat diet. All the mice received intraperitoneal injection of irisin or PBS. Thirty minutes after injection, mice were subjected to 30 min of myocardial ischemia followed by 3h (for cell apoptosis and protein determination), 24 h (for infarct size and cardiac function).

RESULTS

Knock-out of gene FNDC5 augmented MI/R injury in diabetic mice, while irisin treatment attenuated MI/R injury, improved cardiac function, cellular ATP biogenetics, mitochondria potential, and impaired mitochondrion-related cell death. More severely impaired AMPK pathway was observed in diabetic FNDC5 mice received MI/R. Knock-out of gene AMPK blocks the beneficial effects of irisin on MI/R injury, cardiac function, cellular ATP biogenetics, mitochondria potential, and mitochondrion-related cell death.

CONCLUSIONS

Our present study demonstrated that irisin improves the mitochondria function and attenuates MI/R injury in diabetic mice through AMPK pathway.

摘要

目的

最近的几份报告显示,鸢尾素可保护心脏免受缺血/再灌注损伤。然而,鸢尾素对糖尿病小鼠缺血/再灌注损伤的影响尚未见报道。本研究旨在探讨鸢尾素在糖尿病小鼠心肌缺血-再灌注(MI/R)损伤中的作用。

方法

通过给野生型或基因操作的成年雄性小鼠喂食高脂饮食建立糖尿病小鼠模型。所有小鼠腹腔注射鸢尾素或磷酸盐缓冲液(PBS)。注射30分钟后,小鼠经历30分钟的心肌缺血,随后分别在3小时(用于细胞凋亡和蛋白质测定)、24小时(用于梗死面积和心脏功能测定)处死。

结果

基因FNDC5敲除加重了糖尿病小鼠的MI/R损伤,而鸢尾素治疗减轻了MI/R损伤,改善了心脏功能、细胞ATP生成、线粒体电位,并减轻了线粒体相关的细胞死亡。在接受MI/R的糖尿病FNDC5小鼠中观察到AMPK途径受损更严重。基因AMPK敲除阻断了鸢尾素对MI/R损伤、心脏功能、细胞ATP生成、线粒体电位和线粒体相关细胞死亡的有益作用。

结论

我们目前的研究表明,鸢尾素通过AMPK途径改善糖尿病小鼠的线粒体功能并减轻MI/R损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8d3/7516196/833b4242a850/fphar-11-565160-g001.jpg

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