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AIM It has been reported that some polyphenols are able to up-regulate sirtuin 1 (SIRT1) activity, an NAD-dependent deacetylase.Salvianolic acid A(Sal A), an active compound extracted from Salvia mihiorrhiza, is also a phenolic carboxylic acid derivative.The effect of Sal A on the T cell-mediated hepatitis caused by concanavalin A (Con A) has not been carefully explored.In the present study, we aimed to test two hypotheses:① the pretreatment of Sal A can protect mice against Con A-induced acute hepatitis; and ② Sal A prevents mice from Con A-induced acute liver injury via sirtl-p66shc pathway.METHODS Hepatitis was induced in KM mice by administration of Con A(18 mg·kg-1) by tail vein injection for 12 h.Sal A 15 and 25 mg·kg-1 was pretreated intraperitoneally 30 min before Con A administration respectively.The liver function was tested by assessing alanine transaminase (ALT) and aspartate transaminase (AST) activities and histological analysis.While levels of cytokines IFN-γ and TNF-α were measured by ELISA method.The expression of sirt1, p66shc and the relative factors in the downstream mRNA and protein were measured by RT-PCR and Western blot respectively.RESULTS After ConA administration, the activities of serum ALT, AST and the levels of IFN-γ, TNF-α were increased obviously.All of which were all reduced by pretreatment with Sal A.Mean while, Sal A protected against Con A-induced NF-κB and Bcl-xl via remarkable activation of sirtl expression and down-regulation of p66shc adapter protein.CONCLUSION The results suggested that Sal A is a potent activator of sirtl and can alleviate Con A-induced hepatitis via a sirtlp66shc pathway.