Effect Of PI3K? On Hepatic Ischemia Reperfusion Injury In Mice

Objective:To investigate the effect of PI3K?on hepatic ischemia reperfusion injury in mice.Methods:Liver IR model of C57BL/6J mice and H/R model of RAW264.7 mice macrophage were built,and IPI549?PI3K?specific inhibitor?intervention was given.The p110??PI3K??protein in tissues and primary cells were detected by Western blot.The liver injury was determined by serum ALT,HE staining,and TUNEL.The mRNA levels of TNF-?and p110?of RAW264.7 cells during H/R were detected by qRT-PCR.The expression levels of TNF-?,JNK and p-JNK proteins were detected by Western blot,and the levels of TNF-?in cell supernatant were detected by ELISA.Results:Compared with primary hepatocytes,kupffer cells showed significantly higher expression of p110??PI3K??.Compared with sham group,the protein level of p110?in liver tissue of IR group was decreased.Pretreatment with IPI549?PI3K?specific inhibitor?can aggravate liver injury and cell apoptosis after hepatic ischemia reperfusion in mice.Using GdCl₃ to block kupffer cells can alleviate the liver tissue injury and cell apoptosis caused by IPI549.In vitro experiments,the expression level of p110?mRNA decreased during H/R,and the expression level of TNF-?mRNA was further increased after IPI549 intervention.JNK phosphorylation level increased and TNF-?protein expression increased by Western blot.The secretion of TNF-?in cell supernatant is increased by ELISA.Conclusion:Pretreatment with IPI549?PI3K?inhibitor?aggravates hepatic ischemia reperfusion injury in mice,which may be related to the mechanism that IPI549 inhibits the PI3K?of Kupffer cells,affecting the activation of JNK signaling pathway and playing a pro-inflammatory role.