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Life Sci. 2018 Sep 1;208:315-324. doi: 10.1016/j.lfs.2018.05.051. Epub 2018 May 29.

Exogenous hydrogen sulfide ameliorates high glucose-induced myocardial injury & inflammation via the CIRP-MAPK signaling pathway in H9c2 cardiac cells.

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Department of Geriatrics and Cardiovascular Medicine, Shenzhen Sun Yat-Sen Cardiovascular Hospital, Shenzhen 518112, PR China.
Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, PR China.
Department of Geriatrics and Cardiovascular Medicine, Shenzhen Sun Yat-Sen Cardiovascular Hospital, Shenzhen 518112, PR China. Electronic address:



Hydrogen sulfide (H2S) is a novel signaling molecule with potent cytoprotective actions. In this study, we hypothesize that exogenous H2S may protect cardiac cells against high glucose (HG)-induced myocardial injury and inflammation with the involvement of the CIRP-MAPK signaling pathway.


H9c2 cardiac cells cultured under HG conditions were transfected with siRNA and different inhibitor for detecting the effects of sodium hydrogen sulfide (NaHS) (a H2S donor) on cell biological processes. The cardiac cell viability and LDH activity were determined by CCK-8 and LDH kit. ELISA was employed to measure the levels of inflammatory factors, while 2',7'-dichlorofluorescein diacetate (DCFH-DA) to evaluate reactive oxygen species (ROS). Mitochondrial membrane potential (MMP) was identified by rhodamine 123 staining. TUNEL staining and Hoechst 33258 staining were employed to observe cardiac cell apoptosis. Besides, we determined the expression of CIRP-MAPK signaling pathway- and apoptosis-related factors by protein immunoblot analysis.


HG culturing induced toxicity, LDH, higher level of inflammatory factors, ROS, MMP, and apoptosis in cardiac cells, attenuated the viability of cardiac cells, and activated the CIRP-MAPK signaling pathway. Notably, CIRP silencing aggravated the above condition. H2S or blockade of the MAPK signaling pathway reversed the above conditions induced by HG.


The present study provides evidence for the protective effect of exogenous H2S on HG-induced myocardial injury and inflammation in H9c2 cardiac cells and suggests that the activation of CIRP-MAPK signaling pathway might be one of the mechanisms underlying the protective effect of H2S.


Cardiac cells; Cold-inducible RNA-binding protein-mitogen-activated protein kinase signaling pathway; Exogenous hydrogen sulfide; High glucose; Inflammation; Myocardial injury

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