Effect of irisin postconditioning on hepatic ischemia reperfusion injury in rats

Objective To investigate the effect and mechanism of irisin postconditioning on hepatic ischemia reperfusion injury in rats. Methods Totally 36 SD rats were randomly divided into sham group (S), model group (I/R) and irisin group (Ir), with 12 rats in each group. Hepatic ischemia was constructed in model group and irisin group by ligating left middle lobe of liver vascular branches for 60 min. Irisin was administered at the beginning of reperfusion by intravenous injection at the concentration of 10 μg/kg for rats in irisin group. We only dissected the hepatic duodenal ligament of rats in the S group. Serum and liver tissues were collected at 6 h after reperfusion through the inferior chamber. The serum levels of alanine aminotransferase (ALT), glutamic oxalacetic transaminase (AST), interleukin (IL)-6, IL-1βand tumor necrosis factor-α (TNF-α) were examined. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPX) in liver tissue were measured. The pathological changes of liver tissue were observed by hematoxylin and eosin (HE) staining. The phosphorylations of janus kinase 2 (JAK2), signal transducer and activators of transcription 3 (STAT3) and B cell lymphoma/leukemia-2 (bcl-2), bcl-2 associated X protein (bax), cysteinyl aspartate-specific protease (Caspase)-3 were assessed by Western blotting. Results The ALT levels in S group, I/R group and irisin group were as follows: (75.24±2.65), (705.33±4.02), (385.46±3.58) U/L; The AST levels were as follows: (122.33±6.76), (1 357.54±5.23), (738.26±3.98) U/L; The IL-6 levels were as follows: (104±16), (586±86), (275±35) ng/L; The TNF-α levels were as follows: (92±10), (1 165±102), (511±73) ng/L; The IL-1β levels were as follows: (98±12), (610±79), (312±41) ng/L; The MDA contents were as follows: (174±38), (1 900±460), (1 055±266) ng/L; The SOD contents were as follows: (124±10), (46±8), (70±10) ng/L; The GPX contents were as follows: (106±12), (42±5), (62±11) ng/L; The Caspase-3 levels were as follows: (0.22±0.06), (0.86±0.14), (0.57±0.11) ng/L; The p-JAK2 levels were as follows: 0.44±0.05, 0.91±0.07, 0.62±0.11; The p-STAT3 levels were as follows: 0.35±0.04, 0.86±0.08, 0.57±0.07. As compared with the sham group, the levels of ALT, AST, IL-6, TNF-α, IL-1β, MDA and Caspase-3 were significantly increased (t=445.551, 219.362, 21.700, 7.700, 36.182, 14.132, 24.191, 10.111, 13.753, 7.023, 14.456 and 6.556, P<0.01). The activities of GPX and SOD in model group and irisin group were significantly decreased (t=20.374, 14.104, 15.945 and 10.965, P<0.01), and the pathological damage worsened and the expression levels of activated p-JAK2 and p-STAT3were up-regulated in other groups (t=14.289, 5.479, 19.054 and 8.224, P<0.01); As compared with model group, the levels of ALT, AST, IL-6, TNF-α, IL-1β, MDA and Caspase-3 in irisin group were significantly decreased (t=226.183, 14.000, 14.081, 22.052 and 7.906, P<0.01), and pathological damage was alleviated and the expression levels of activated SOD and GPX significantly increased (t=6.274 and 4.985, P<0.01). The p-JAK2 and p-STAT3 were down-regulated in irisin group (t=8.819 and 10.834, P<0.01). Conclusion Exogenous irisin postconditioning can significantly decrease hepatic ischemia-reperfusion injury in rats by suppressing oxidative stress and cell apoptosis, and the mechanism may be associated with the suppression of JAK2/STAT3 signaling activation. Key words: Irisin; Hepatic ischemia; Reperfusion injury; Janus kinase 2; Signal transducer and activators of transcription 3