Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany.
Department of Radiotherapy and Radiooncology, Jena University Hospital, Jena, Germany.
Sci Rep. 2020 Mar 17;10(1):4893. doi: 10.1038/s41598-020-60310-0.
The liver has the ability to maintain its total size by adjusting the size of the individual liver lobes differently in response to regeneration- and atrophy-stimuli. Portal vein ligation (PVL) drives the ligated lobe to undergo atrophy whereas partial hepatectomy (PHx) drives the total remnant liver to regenerate. We hypothesize that the size of the PVL-lobe is dependent on the balance between the extent of PVL and the extent of PHx inducing a complex interplay between hepatocyte proliferation, apoptosis and autophagy. Lewis-rats were subjected to either 20%PVL + 70%PHx or 70%PVL + 20%PHx. Control groups consisted of 20%PVL and 70%PVL. Liver lobe weight, BrdU-proliferation-index, proliferating-cell-nuclear-antigen-mRNA-expression level, apoptotic density and autophagy-related-proteins were investigated. The PVL-liver lobe adjusted its weight differently, increasing by 40% after 20%PVL + 70%PHx, but decreasing by 25% after 70%PVL + 20%PHx. Additional resection induced a low, but substantial size-dependent hepatocyte proliferation rate (maximal 6.3% and 3.6% vs. 0.3% and significantly suppressed apoptotic density in the deportalized-liver-lobe (3 and 14 cells/mm comparing with above 26 cells/mm, p < 0.01). Autophagy was more activated in PVL-liver lobe after simultaneous PHx than after PVL only. In summary, atrophy of the PVL-liver lobe after simultaneous PHx was counteracted by promoting hepatocyte proliferation, inducing autophagy and suppressing apoptosis in a PHx-extent-dependent manner.
肝脏具有通过调整各个肝叶的大小来维持其总体大小的能力，这种调整是对再生和萎缩刺激的反应。门静脉结扎（PVL）导致结扎的肝叶发生萎缩，而部分肝切除术（PHx）则促使总残余肝脏再生。我们假设 PVL 叶的大小取决于 PVL 程度和 PHx 程度之间的平衡，这会导致肝细胞增殖、凋亡和自噬之间的复杂相互作用。Lewis 大鼠接受 20%PVL+70%PHx 或 70%PVL+20%PHx 处理。对照组包括 20%PVL 和 70%PVL。研究了肝叶重量、BrdU 增殖指数、增殖细胞核抗原 mRNA 表达水平、凋亡密度和自噬相关蛋白。PVL 肝叶以不同的方式调整其重量，在 20%PVL+70%PHx 后增加 40%，但在 70%PVL+20%PHx 后减少 25%。额外的切除诱导了一个低但与肝叶大小相关的实质性肝细胞增殖率（最大为 6.3%和 3.6%，而 0.3%，并且明显抑制了门静脉结扎肝叶中的凋亡密度（3 和 14 个细胞/mm，与以上 26 个细胞/mm 相比，p<0.01）。在同时进行 PHx 后，PVL 肝叶中的自噬比仅进行 PVL 时更为活跃。总之，同时进行 PHx 后，PVL 肝叶的萎缩通过促进肝细胞增殖、诱导自噬和以 PHx 程度依赖的方式抑制凋亡来抵消。
