Protective Effects of Necrostatin-1 against Concanavalin A-Induced Acute Hepatic Injury in MiceReportar como inadecuado




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Mediators of InflammationVolume 2013 2013, Article ID 706156, 15 pages

Research ArticleDepartment of Gastroenterology, The Tenth People-s Hospital of Tongji University, Shanghai 200072, China

Received 19 April 2013; Revised 15 July 2013; Accepted 14 August 2013

Academic Editor: Muzamil Ahmad

Copyright © 2013 Yingqun Zhou et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective. Necrostatin-1 Nec-1 inhibits receptor-interacting protein 1 RIP1 kinase and programmed necrosis. This study was designed to examine the protective effects and mechanisms of Nec-1 in concanavalin A- ConA- induced hepatitis in mice. Methods. C57BL-6 mice were exposed to ConA via tail vein injection and injected intraperitoneally with Nec-1 or vehicle. Levels of serum liver enzymes and histopathology were determined. Levels of inflammatory cytokines with ConA-induced hepatitis were determined with real-time polymerase chain reaction real-time PCR. The expression of TNF-α, RIP1, and LC3 was detected with immunohistochemical staining. The expression of TNF-α, IFN-γ, IL2, IL6, caspase 3, RIP1, beclin-1, and LC3 protein was assessed by immunofluorescence and western blotting. Autophagosomes were observed with transmission electron microscopy TEM. Results. Amelioration in liver functions and histopathological changes and thesuppression of inflammatory cytokine production were observed in Nec-1-injected mice. Western blotting analysis showed that the expression of TNF-α, IFN-γ, IL2, IL6, and RIP1 was significantly reduced in the Nec-1-injected mice, which was confirmed by immunofluorescence and immunohistochemistry. Autophagosome formation was significantly reduced by Nec-1 treatment, as the expression of beclin-1 and LC3, determined with immunofluorescence and western blotting. Conclusion. These results demonstrate that Nec-1 prevents ConA-induced liver injury via RIP1-related and autophagy-related pathways.





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