Abstract:

Objective To explore the influence of Atractylidene Ⅲ（Atr⁃Ⅲ）on liver injury in septic rats and its regulation on AMP⁃activated protein kinase（AMPK）/ sirtuin 1（SIRT1）/nuclear factor kappa⁃B（NF⁃κB） signaling pathway. Methods Eighty SPF SD male rats were randomly grouped into sham operation group，model group，positive group，low⁃dose，high⁃dose Atr⁃Ⅲ group，and high⁃dose Atr⁃Ⅲ+AMPK inhibitor group. The levels of aspartate aminotransferase（AST）and alanine aminotransferase（ALT）were detected in the serum of rats；HE staining was applied to observe the pathological changes of liver tissue；TUNEL staining was applied to detect hepa⁃ tocyte apoptosis；ELISA was applied to detect the levels of serum interleukin 1β（IL⁃1β），interleukin 6（IL⁃6）， tumor necrosis factor α（TNF⁃α）；the activities of superoxide dismutase（SOD）and catalase（CAT）liver tissue were detected；Western blot was used to detect the expression of related proteins. Results Compared with sham operation group，hepatocyte injury was severe in model group，the levels of AST，ALT，IL⁃1β，IL⁃6，TNF⁃α，the rate of apoptosis，and the ratio of p⁃p65 NF⁃κB/p65 NF⁃κB were all increased（P < 0.05），the levels of SOD， CAT，the ratio of p⁃AMPK/AMPK，and the protein expression of SIRT1 were all decreased（P < 0.05）. Compared with model group，the morphology of rat hepatocytes in positive group and Atr⁃Ⅲ low⁃dose and high⁃dose groups recovered，the levels of AST，ALT，IL⁃1β，IL⁃6，TNF⁃α，the rate of apoptosis，and phosphorylation of p65 NF⁃ κB were all increased（P < 0.05），the levels of SOD，CAT，phosphorylation of AMPK，and the protein expression of SIRT1 were all decreased（P < 0.05）. The AMPK inhibitor BML⁃275 abrogated the attenuating effect of high⁃ dose ATL⁃Ⅲ on liver injury in septic rats. Conclusion Atr⁃Ⅲ can activate the AMPK/SIRT1 signaling pathway and inhibit the activation of p65 NF⁃κB，thereby reducing liver injury in septic rats. 

Key words:

Atractylenolide Ⅲ, AMPK/SIRT1/NF?κB pathway, sepsis, liver injury, inflammation