Vitamin B12 alleviates myocardial ischemia/reperfusion injury via the SIRT3/AMPK signaling pathway

作者全名："Qin, Yuhong; Shi, Yani; Yu, Qi; Yang, Shenglan; Wang, Ying; Dai, Xiaojia; Li, Guoxing; Cheng, Zhe"

作者地址："[Qin, Yuhong] Chongqing Univ, Fuling Hosp, Dept Hepatol & Translat Med, Chongqing 400016, Peoples R China; [Shi, Yani] Chongqing Univ Fuling Hosp, Dept Gen Med, Chongqing 400016, Peoples R China; [Yu, Qi; Yang, Shenglan; Wang, Ying] Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiol, Chongqing 400016, Peoples R China; [Dai, Xiaojia] Southwest Med Univ, Clin Med Coll, Luzhou 646099, Sichuan, Peoples R China; [Li, Guoxing; Cheng, Zhe] Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China; [Cheng, Zhe] Chongqing Univ Three Gorges Hosp, Dept Cardiol, Chongqing, Peoples R China; [Cheng, Zhe] Chongqing Three Gorges Cent Hosp, Chongqing 404000, Peoples R China"

通信作者："Li, GX; Cheng, Z (通讯作者)，Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China."

来源：BIOMEDICINE & PHARMACOTHERAPY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000991286700001

JCR分区：Q1

影响因子：6.9

年份：2023

卷号：163

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Myocardial ischemia; reperfusion injury; Vitamin B12; SIRT3; AMPK

摘要："Aim: To examine the protective effect of vitamin B12 against myocardial ischemia/reperfusion (I/R) injury and elucidate its underlying mechanism of action.Methods: Mice were subjected to myocardial I/R injury by left anterior descending coronary artery (LAD) oc-clusion followed by 24 h reperfusion. Cardiac function and injury were evaluated by echocardiography, triphenyl tetrazolium chloride (TTC) and cardiac troponin T (cTnT) staining, and measuring lactate dehydrogenase (LDH) levels. In addition, various molecular and biochemical methods, as well as RNA sequencing were used to determine the effects and mechanism of action of vitamin B12 on I/R injury.Results: We found that high doses of vitamin B12 inhibited myocardial I/R injury. Furthermore, our data indi-cated that vitamin B12 supplementation alleviated cardiac dysfunction and injury by mitigating oxidative stress and apoptosis through downregulation of Nox2, the Ac-SOD2/SOD2 and Bax/Bcl-2 ratios and cleaved caspase-3 expression, and upregulation of SIRT3 expression and AMPK activity. However, these effects were largely reversed following treatment with the SIRT3 inhibitor, 3-TYP. Our RNA-sequencing data further demonstrated that vitamin B12 supplementation reduced inflammation during I/R injury.Conclusion: High doses of vitamin B12 supplements improved myocardial I/R injury by suppressing the accu-mulation of reactive oxygen species and apoptosis of myocardial tissue through modulation of the SIRT3/AMPK signaling pathway, while reducing inflammation. Our findings suggested that vitamin B12 administered at high doses could be a potential therapy for myocardial I/R damage."

基金机构：Doctoral Research Start-up Fund of Chongqing University Three Gorges Hospital & Chongqing Three Gorges Central Hospital [2022YJKYXM-039]; Chongqing Natural Science Foundation of Postdoctoral Program [CSTB2022NSCQ-BHX0712]

基金资助正文：This study was supported by the Doctoral Research Start-up Fund of Chongqing University Three Gorges Hospital & Chongqing Three Gorges Central Hospital (2022YJKYXM-039) and the Chongqing Natural Science Foundation of Postdoctoral Program (CSTB2022NSCQ-BHX0712).