| [Objective] To investigate the potential regulatory role of protein phosphatase 2A(PP2A) in the expression of nuclear factor-κB (NF-κB) and its effective mechanism in the acute liver injury induced by sepsis, and provide guidelines of prevention and therapy for that.[Methods] Sepsis associated acute liver injury was produced in rats by cecal ligation and puncture(CLP).The rats were devided randomly into three groups,e.g.CLP group, Pyrrolidine dithiocarbamate(PDTC) treated group,and sham operated group. Twenty-four hours after the operation, pathologic changes were examined under optical microscope, and the index of liver function such as ALT,AST,STB and UCB were determined, and the expression changes of NF-κB, PP2A and tumor necrosis factor-α(TNF-α) in liver tissue were detected by RT-PCR and enzyme-linked immunosorbent assay, respectively.[Results] The sepsis induced by CLP resulted in acute liver pathologic injury. Compared to sham operated group,both the expression of NF-κB and TNF-αin liver tissue were significantly increased in rats with sepsis induced by CLP,and the index of liver function increased accordingly, but the expression of PP2A was higher in the sham operated group; And the NF-κB activity and TNF-αlevel in liver tissue,and the index of liver function degraded in PDTC treated group, but the expression of PP2A enhanced obviously reversely.[Conclusions] (1)The sepsis can lead to acute liver injury. (2) Sepsis could result in NF-κB activation and NF-κB associated up regulation of liver TNF-αexpression in rats with acute liver injury ,and this enhancement property maybe relate to the suppressed expression of PP2A. (3)And PDTC, the inhibitor of NF-κB can depress the expression of TNF-αin hepatic tissue which stimulated by sepsis and can improve the acute liver injury induced by sepsis, and this depressant effect may have something to do with the up-regulation of PP2A.PP2A may play a regulatory role in NF-κB activation of acute liver injury induced by sepsis.
|
PDF Full Text Request