Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, P.R. China.
Department of Pathophysiology, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
Mol Med Rep. 2018 Apr;17(4):5390-5395. doi: 10.3892/mmr.2018.8522. Epub 2018 Jan 30.
Liver regeneration post severe liver injury is crucial for the recovery of hepatic structure and function. The energy sensor AMP‑activated protein kinase (AMPK) has a crucial role in the regulation of nutrition metabolism in addition to other energy‑intensive physiological and pathophysiological processes. Cellular proliferation requires intensive energy and nutrition support, therefore the present study investigated whether AMPK is involved in liver regeneration post carbon tetrachloride (CCl4)‑induced acute hepatic injury. The experimental data indicated that phosphorylation level of AMPK increased 48 h post‑CCl4 exposure, which was accompanied with upregulation of proliferating cell nuclear antigen (PCNA) and recovery of alanine aminotransferase (ALT) level. Pretreatment with the AMPK inhibitor compound C had no obvious effects on ALT elevation in plasma and histological abnormalities in liver 24 h post CCl4 exposure. However, treatment with compound C 24 h post CCl4 exposure significantly suppressed CCl4‑induced AMPK phosphorylation, PCNA expression and ALT recovery. These data suggest that endogenous AMPK was primarily activated at the regeneration stage in mice with CCl4‑induced acute liver injury and may function as a positive regulator in liver regeneration.
严重肝损伤后肝脏的再生对于恢复肝脏结构和功能至关重要。除了其他能量密集型生理和病理生理过程外，能量传感器 AMP 激活的蛋白激酶 (AMPK) 在营养代谢的调节中也起着关键作用。细胞增殖需要密集的能量和营养支持，因此本研究探讨了 AMPK 是否参与四氯化碳 (CCl4) 诱导的急性肝损伤后的肝脏再生。实验数据表明，CCl4 暴露后 48 小时 AMPK 的磷酸化水平增加，同时增殖细胞核抗原 (PCNA) 上调，丙氨酸氨基转移酶 (ALT) 水平恢复。在 CCl4 暴露后 24 小时用 AMPK 抑制剂化合物 C 预处理对血浆中 ALT 升高和肝脏组织学异常没有明显影响。然而，在 CCl4 暴露后 24 小时用化合物 C 处理可显著抑制 CCl4 诱导的 AMPK 磷酸化、PCNA 表达和 ALT 恢复。这些数据表明，内源性 AMPK 在 CCl4 诱导的急性肝损伤小鼠的再生阶段主要被激活，并且可能在肝脏再生中作为正调节剂发挥作用。
