Protection Of Gentiopicroside On Acute Liver Injury Of Mice Induced By Sepsis

Objective To investigate the protective effects of Gentiopicroside onsepsis-induced acute liver injury in mice.Method Sepsis-induced acute liver injury was induced by cecalligation and puncture(CLP).Forty KunMing male mice were randomlydivided into four groups as sham operation group, CLP model group,CLP＋Gentiopicroside (25mg/kg,50mg/kg) groups. CLP model group and shamoperation group animals accepted a separate tail intravenous injection ofnormal saline, CLP＋Gentiopicroside groups received tail intravenousinjection of Gentiopicroside(25mg/kg,50mg/kg) At30minutes before CLP.General activities of the animals were observed after CLP.Tumor necrosisfactor alpha(TNF-α) and interleukin6(IL-6) in serum were assayedby enzyme-linked immunorrbent assay(ELISA). Alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels in serum, the levels ofnitric oxide(NO) and malondialdehyde(MDA), the activity of inducibleoxide synthase(iNOS) and myeloperoxidase(MPO) in liver were detectedby the biochemistry method. The histopathological changes in liver wereobserved under light microscope via hematoxylin-eosin (HE) stain. NOD1， NOD2mRNA expressions in liver were detected by RT-PCR and NF-κBprotein expressions in liver were detected by Western-blotting.Results The results showed that the serum concentration of pro-inflammatory cytokine(TNF-α,IL-6), ALT and AST were increasedsignificantly in CLP model group as compared with the sham operationgroup at12h after CLP. Meanwhile, the levels of NO， iNOS，MDA andMPO in liver tissues increased obviously, a mount of vacuolar degenerationof hepatic cells and inflammatory cells were observed in the liver tissuesunder light microscope. In comparision with the model group, Gentiopic-oside could significantly decrease the levels of pro-inflammatory cytokine(TNF-α,IL-6),ALT and AST in serum, reduce the levels of NO and MDA,the activity of iNOS and MPO in liver, improve histopathological changesin liver, especially at the dose of50mg/kg. Western blot and RT-PCRmethods to detect the liver tissue and the results showed that theexpression of NF-κB protein and NOD1，NOD2mRNA were up-regulatedsignificantly in CLP model group, Gentiopicoside (25mg/kg,50mg/kg)could obviously down-regulated the over expression of NF-κB proteinand NOD1，NOD2mRNA.Conclusion These results suggest that Gentiopicroside would have aprotective effect on CLP-induced acute liver injury,and the effect isprobably associated with the inhibition of the over expression of NOD1andNOD2,preventing NF-κB activating,reducing inflammatory response and oxidation reaction.