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利拉鲁肽通过激活硫化氢和核因子红细胞 2 相关因子 2 信号通路恢复糖尿病大鼠的晚期心脏保护作用。

Liraglutide restores late cardioprotective effects of remote preconditioning in diabetic rats via activation of hydrogen sulfide and nuclear factor erythroid 2-related factor 2 signaling pathway.

机构信息

MM. Jiangxi Provincial People's Hospital - Department of Cardiology - Nanchang, (Jiangxi), China.

MM. The Forth People's Hospital of Yongzhou - Department of Cardiovascular Medicine - Yangzhou (Hunan), China.

出版信息

Acta Cir Bras. 2021 Feb 26;36(2):e360207. doi: 10.1590/ACB360207. eCollection 2021.

DOI:10.1590/ACB360207
PMID:33656046
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7909944/
Abstract

PURPOSE

The present study explored the influence of liraglutide on remote preconditioning-mediated cardioprotection in diabetes mellitus along with the role of nuclear factor erythroid 2-related factor 2 (Nrf2), hypoxia inducible factor (HIF-1α) and hydrogen sulfide (H2S).

METHODS

Streptozotocin was given to rats to induce diabetes mellitus and rats were kept for eight weeks. Four cycles of ischemia and reperfusion were given to hind limb to induce remote preconditioning. After 24 h, hearts were isolated and subjected to 30 min of ischemia and 120 min of reperfusion on Langendorff system. Liraglutide was administered along with remote preconditioning. Cardiac injury was assessed by measuring the release of creatine kinase (CK-MB), cardiac troponin (cTnT) and development of left ventricular developed pressure. After ischemia-reperfusion, hearts were homogenized to measure the nuclear cytoplasmic ratio of Nrf2, H2S and HIF-1α levels.

RESULTS

In diabetic rats, there was more pronounced injury and the cardioprotective effects of remote preconditioning were not observed. Administration of liraglutide restored the cardioprotective effects of remote preconditioning in a dose-dependent manner. Moreover, liraglutide increased the Nrf2, H2S and HIF-1α levels in remote preconditioning-subjected diabetic rats.

CONCLUSIONS

Liraglutide restores the lost cardioprotective effects of remote preconditioning in diabetes by increasing the expression of Nrf2, H2S and HIF-1α.

摘要

目的

本研究探讨了利拉鲁肽对糖尿病患者远程预处理介导的心脏保护作用及其与核因子红细胞 2 相关因子 2（Nrf2）、缺氧诱导因子（HIF-1α）和硫化氢（H2S）的关系。

方法

给予链脲佐菌素诱导大鼠糖尿病，并饲养 8 周。对后肢进行 4 个周期的缺血再灌注，以诱导远程预处理。24 h 后，在 Langendorff 系统上分离心脏，进行 30 min 缺血和 120 min 再灌注。给予利拉鲁肽联合远程预处理。通过测量肌酸激酶（CK-MB）、心肌肌钙蛋白（cTnT）的释放和左心室发展压的变化来评估心脏损伤。缺血再灌注后，心脏匀浆用于测量 Nrf2、H2S 和 HIF-1α水平的核质比。

结果

在糖尿病大鼠中，损伤更为明显，且远程预处理的心脏保护作用未观察到。利拉鲁肽给药以剂量依赖的方式恢复了远程预处理的心脏保护作用。此外，利拉鲁肽增加了远程预处理糖尿病大鼠的 Nrf2、H2S 和 HIF-1α水平。

结论

利拉鲁肽通过增加 Nrf2、H2S 和 HIF-1α的表达，恢复了糖尿病患者远程预处理失去的心脏保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d338/7909944/d098a3e24085/1678-2674-acb-36-2-e360207-gf06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d338/7909944/40bb5e806222/1678-2674-acb-36-2-e360207-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d338/7909944/2fab6506d1c5/1678-2674-acb-36-2-e360207-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d338/7909944/98bf24ec6731/1678-2674-acb-36-2-e360207-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d338/7909944/02702d6ff7ef/1678-2674-acb-36-2-e360207-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d338/7909944/9fe59246d383/1678-2674-acb-36-2-e360207-gf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d338/7909944/d098a3e24085/1678-2674-acb-36-2-e360207-gf06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d338/7909944/40bb5e806222/1678-2674-acb-36-2-e360207-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d338/7909944/2fab6506d1c5/1678-2674-acb-36-2-e360207-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d338/7909944/98bf24ec6731/1678-2674-acb-36-2-e360207-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d338/7909944/02702d6ff7ef/1678-2674-acb-36-2-e360207-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d338/7909944/9fe59246d383/1678-2674-acb-36-2-e360207-gf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d338/7909944/d098a3e24085/1678-2674-acb-36-2-e360207-gf06.jpg

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Role of O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins in diabetic cardiovascular complications.蛋白质的 O-连接 N-乙酰葡萄糖胺（O-GlcNAc）修饰在糖尿病心血管并发症中的作用。
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