Abstract：
:Sepsis induced myocardial dysfunction (SIMD) results in high morbidity and mortality. However, the effective therapeutic strategies for SIMD treatment remain limited. Sirt3 is the main mitochondrial Sirtuin member and is a key modulator of mitochondrial metabolism and function. In this study, we aimed to investigate the effect and mechanism of Sirt3 on SIMD. SIMD was induced by 20 mg/kg Lipopolysaccharides (LPS) injection for 6 h in mice. Sepsis could induce the reduction of cardiac Sirt3 expression and global deficiency of Sirt3 exacerbated cardiac function. Quantitative acetyl-proteomics and cardiac metabolomics analysis revealed that loss of Sirt3 led to hyper-acetylation of critical enzymes within cardiac tricarboxylic acid (TCA) cycle and generation of lactate and NADH, subsequently promotion of cardiac dysfunction after sepsis. Additionally, to evaluate whether Emodin could be utilized as a potential Sirt3 modulator to treat SIMD, male wild type mice (WT mice) or global Sirt3 deficient mice (Sirt3-/- mice) were intraperitoneally injected with 40 mg/kg Emodin for 5 days followed by 20 mg/kg LPS administration for another 6 h and observed that exogenous administration of Emodin could attenuate myocardial dysfunction in septic WT mice. However, septic Sirt3-/- mice can not gain benefit on cardiac performance from Emodin infusion. In conclusion, this study presented the protective role of Sirt3 targeting SIMD, which may provide a potential novel approach to maintain normal cardiac performance after sepsis.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Xu Y,Zhang S,Rong J,Lin Y,Du L,Wang Y,Zhang Zdoi
10.1016/j.phrs.2020.104887subject
Has Abstractpub_date
2020-09-01 00:00:00pages
104887eissn
1043-6618issn
1096-1186pii
S1043-6618(20)31195-6journal_volume
159pub_type
杂志文章abstract：:The interaction of mianserin with ethanol in central nervous system (CNS) was investigated. Mianserin was administered at a single dose of 5 or 20 mgkg(-1) i.p. or as daily injections in a dose of 2.5 mgkg(-1) given for 14 days. The influence of mianserin on acute ethanol toxicity (LD(50)), on ED(50) of ethanol in rot...
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journal_title：Pharmacological research
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更新日期：2019-11-01 00:00:00
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更新日期：2013-10-01 00:00:00
