Protective effect of IL-33 preconditioning on hepatic ischemia reperfusion injury in mice

Objective To explore the effects of interleukin(IL)-33 preconditioning on hepatic ischemia reperfusion in mice, and its possible mechanism.

MethodsForty-five male C57BL/6 mice were randomly divided into the sham operation group(Sham group), ischemia and reperfusion injury group(PBS+I/R group, control group) and IL-33+ischemia and reperfusion injury group(rIL-33+I/R group)(15 mice each group).The hepatic artery and portal vein and bile duct of left, middle and caudate lobe of liver in control group were separated, and blocked using no injury microvascular clip for 60 min after 1 h of intravenous injection of the same amount of phosphate buffer.The hepatic artery and portal vein and bile duct of left, middle and caudate lobe of liver in experimental group(rIL-33+I/R group) were separated, and blocked using no injury microvascular clip for 60 min after 1 h of intravenous injection of recombinant IL-33 protein.The treatment of the sham operation group(Sham group) was the same as the control group except for no using no injury microvascular clip.Each group was divided into three subgroups(5 mice each subgroup), the serum levels of ALT, AST and IL-17, and expression levels of IL-33 and myeloperoxidase(MPO) in ischemic liver tissue were detected after 6 h, 12 h and 24 h of reperfusion.

Results The expression of IL-33 in muse liver significantly increased during liver ischemia and reperfusion.After 12 h of reperfusion, the serum levels of ALT and AST in PBS+I/R group significantly increased compared with the Sham group(P < 0.01), and the serum levels of ALT and AST in rIL-33+I/R group significantly decreased compared with the PBS+I/R group(P < 0.01).The Results of HE staining in rIL-33+I/R group showed that the hepatocyte damaged, the neutrophil infiltration was found, and the MPO content in liver tissue was significantly lower than that in PBS+I/R group(P < 0.01).The Results of ELISA showed that the serum levels of IL-17A in rIL-33+I/R group was significantly lower than that in PBS+I/R group(P < 0.01).

Conclusions IL-33 can protect the hepatic ischemia reperfusion injury in mouse, the mechanism of which may be related to the inhibition of IL-17A expression and reduction of neutrophil infiltration.