Inserm U522, CHU Pontchaillou, Rue Henri Le Guilloux, Rennes, France.
J Hepatol. 2010 Apr;52(4):560-9. doi: 10.1016/j.jhep.2010.01.013. Epub 2010 Feb 13.
BACKGROUND & AIMS: Liver resection includes temporal vascular inflow occlusion resulting in ischemia/reperfusion injury in the remnant liver. Here, we developed a rat model of selective lobe occlusion to isolate reperfusion stress from ischemia and to analyze its effect on liver regeneration.
Left lateral and median lobes of liver were either mobilized or subjected twice for 10min to ischemia followed by 5min reperfusion prior to resection while the regenerative lobes were only subjected to reperfusion.
Although intermittent reperfusion stress induced higher levels of serum transaminases, analysis of cell cycle regulators revealed accelerated regenerative response compared to standard partial hepatectomy. The G0/G1 transition occurred before tissue resection, as evidenced by c-fos, junB, and IL-6 induction. Following hepatectomy, Cyclin D1 up-regulation, G1/S transition, and cell division occurred earlier than normal. Unexpectedly, liver mobilization, a component of the clamping procedure, also resulted in earlier G1/S transition. The shortened G1-phase was driven by the c-Jun N-terminal Kinase pathway and was associated with an oxidative stress response as evidenced by the expression of inducible nitric oxide synthase.
Intermittent selective clamping of lobes to be resected induced reperfusion stress on remnant liver that was beneficial for liver regeneration, suggesting this procedure could be applied in clinical practice.
肝切除术包括暂时的血管流入闭塞，导致剩余肝脏发生缺血/再灌注损伤。在这里，我们开发了一种大鼠选择性肝叶阻断模型，将再灌注应激与缺血分离，并分析其对肝再生的影响。
将左外侧和中叶要么移动，要么两次进行 10 分钟的缺血，然后进行 5 分钟的再灌注，然后再进行切除，而再生叶只进行再灌注。
尽管间歇性再灌注应激导致血清转氨酶水平升高，但对细胞周期调节剂的分析显示，与标准部分肝切除术相比，再生反应更快。组织切除前发生 G0/G1 过渡，证据是 c-fos、junB 和 IL-6 的诱导。肝切除后，Cyclin D1 的上调、G1/S 过渡和细胞分裂比正常情况下更早发生。出乎意料的是，肝移动，即夹闭过程的一部分，也导致了更早的 G1/S 过渡。缩短的 G1 期是由 c-Jun N-末端激酶途径驱动的，与氧化应激反应有关，证据是诱导型一氧化氮合酶的表达。
将要切除的肝叶间歇性选择性夹闭会对剩余肝脏产生再灌注应激，有利于肝再生，这表明该方法可在临床实践中应用。
