Combined kidney‑liver perfusion enhances the proliferation effects of hypothermic perfusion on liver grafts via upregulation of IL‑6/Stat3 signaling

肾肝联合灌注通过上调 IL-6/Stat3 信号增强低温灌注对肝移植物的增殖作用

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作者:Jianhui Li, Junjun Jia, Ning He, Li Jiang, Hao Yu, Haoyu Li, Yifan Peng, Haiyang Xie, Lin Zhou, Shusen Zheng

Methods

A total of 12 rats were randomly assigned into two groups (n=6 for each group): The kidney‑liver perfusion (KL) group and liver perfusion (LP) group. Perfusate samples were collected during the perfusion process for the analysis of pH, K+ and liver function. Liver tissues were obtained for the evaluation of adenosine triphosphate (ATP), terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labelling and immunohistochemistry of Ki67. Cell cycle inhibitors, apoptosis‑associated genes and signal transducer and activator of transcription 3 (Stat3) were analyzed using quantitative polymerase chain reaction and western blot analysis.

Results

Overall pH and K+ values of the KL group were significantly different from the LP group and more stable; aspartate aminotransferase, alanine transaminase and lactate dehydrogenase levels increased progressively over time in the LP group and were significantly different at different time points compared with pre‑perfusion levels and the KL group, which suggested the KL group was superior to the LP group. In addition, KL reduced portal vein resistance and was associated with lower ATP consumption compared with the LP group. Furthermore, liver proliferation was upregulated with the upregulation of the interleukin 6 (IL‑6)/Stat3 signaling pathway in KL compared with LP. The present study revealed for the first time that KL and hypothermic machine perfusion demonstrated a more proactive repair capability by maintaining liver regeneration via the upregulation of the IL‑6/Stat3 signaling pathway.

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