Effect of JAK2/STAT1 on acute kidney injury induced by liver cold ischemia reperfusion in rats

Objective To investigate the effect of Janus kinase2/signal transducer and activator of transcription 1 (JAK2/STAT1) signaling pathway on acute kidney injury induced by liver cold ischemia reperfusion (IR) in rats. Methods Thirty healthy male Sprague-Dawley rats, weighing 220-250 g, were assigned randomly to 3 groups (n=10/group): sham operation group (Sham group); liver cold ischemia reperfusion model group (I/R group); JAK2 kinase inhibitor AG490 group (AG490 group) (AG490 at dose of 10 mg/kg was intraperitoneally injected 30 min before establishment of the model). Other groups were given the equal volume of normal saline at the same time points. Then the rats were sacrificed at 6 h after reperfusion (at 6 h after the end of operation in Sham group). The renal function and oxidative stress level were observed. The pathological changes of the renal tissues and nephritic cell apoptosis were analyzed, and the expression of p-JAK2, p-STAT1, Bcl-2 and Bax was detected by Western blotting. Results As compared with Sham operation group, renal histological lesion and renal dysfunction were aggravated, level of oxidative stress and apoptosis rate were increased in I/R group, the Bcl-2/Bax ratio was decreased and the expression of p-JAK2 and p-STAT1 was up-regulated.As compared with I/R group, AG490 dramatically attenuated histological lesions and oxidative stress, restored the renal function, and reduced the number of apoptotic tubular epithelial cells. AG490 significantly increased the Bcl-2/Bax ratio, and inhibited the expression of p-JAK2 and p-STAT1. Conclusion Blockage of JAK2/STAT1 signaling pathway can alleviate acute kidney injury after liver cold ischemia reperfusion probable through inhibiting the oxidative stress and apoptosis. Key words: Rats; Liver; Ischemia reperfusion; JAK/STAT pathway; Kidney injury