Protective Effects of Inhibition of Mitochondrial Fission on Organ Function After Sepsis.

Autor:	Zhu Y; State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China., Kuang L; State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China., Wu Y; State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China., Deng H; State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China., She H; State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China., Zhou Y; State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China., Zhang J; State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China., Liu L; State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China., Li T; State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2021 Sep 08; Vol. 12, pp. 712489. Date of Electronic Publication: 2021 Sep 08 (Print Publication: 2021).
DOI:	10.3389/fphar.2021.712489
Abstrakt:	Sepsis-associated organ dysfunction plays a critical role in its high mortality, mainly in connection with mitochondrial dysfunction. Whether the inhibition of mitochondrial fission is beneficial to sepsis-related organ dysfunction and underlying mechanisms are unknown. Cecal ligation and puncture induced sepsis in rats and dynamic related protein 1 knockout mice, lipopolysaccharide-treated vascular smooth muscle cells and cardiomyocytes, were used to explore the effects of inhibition of mitochondrial fission and specific mechanisms. Our study showed that mitochondrial fission inhibitor Mdivi-1 could antagonize sepsis-induced organ dysfunction including heart, vascular smooth muscle, liver, kidney, and intestinal functions, and prolonged animal survival. The further study showed that mitochondrial functions such as mitochondrial membrane potential, adenosine-triphosphate contents, reactive oxygen species, superoxide dismutase and malonaldehyde were recovered after Mdivi-1 administration via improving mitochondrial morphology. And sepsis-induced inflammation and apoptosis in heart and vascular smooth muscle were alleviated through inhibition of mitochondrial fission and mitochondrial function improvement. The parameter trends in lipopolysaccharide-stimulated cardiomyocytes and vascular smooth muscle cells were similar in vivo . Dynamic related protein 1 knockout preserved sepsis-induced organ dysfunction, and the animal survival was prolonged. Taken together, this finding provides a novel effective candidate therapy for severe sepsis/septic shock and other critical clinical diseases. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Zhu, Kuang, Wu, Deng, She, Zhou, Zhang, Liu and Li.)
Databáze:	MEDLINE
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