Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany.
Department of Visceral-, Transplant-, Thoracic- and Vascular Surgery, University Clinic Leipzig, Liebigstraße 20, Haus 4, 04103, Leipzig, Germany.
Sci Rep. 2021 Jun 3;11(1):11740. doi: 10.1038/s41598-021-90819-x.
Portal vein ligation (PVL) has been adopted to induce hypertrophy of the future liver remnant (FLR) in patients with primarily irresectable liver tumor. However, regeneration of the FLR is not always sufficient to allow curative resection of the portally-deprived tumor-bearing liver lobe. We hypothesize that simultaneous hepatectomy (PHx) and PVL augments regeneration of the FLR and that the effect is related to the extent of the additional resection. Seventy-two Lewis rats were enrolled into 3 groups: 20%PVL + 70%PHx; 70%PVL + 20%PHx; 90%PVL. Animals were observed for 1, 2, 3 and 7 days postoperatively (n = 6/time point). Liver enzymes, caudate liver/body-weight-ratio, BrdU-proliferation-index (PI), proliferating-cell-nuclear-antigen (PCNA)-mRNA-expression level and autophagy-related-proteins were evaluated. Compared with 90% PVL, additional PHx induced significantly more hypertrophy during the observation time, which was confirmed by significantly higher PI and higher level of PCNA-mRNA expression. Similarly, the additional PHx induced more autophagy in the FLR compared with PVL alone. However, both effects were not clearly related to the extent of additional resection. Additional resection augmented liver regeneration and autophagy substantially compared with PVL alone. Therefore, we concluded that autophagy might play a critical role in regulating hepatocyte proliferation and the size of the FLR after simultaneous PVL + PHx.
门静脉结扎术(PVL)已被用于诱导主要不可切除的肝肿瘤患者的未来肝残余物(FLR)的肥大。然而,FLR 的再生并不总是足以允许对门静脉剥夺的肿瘤性肝叶进行治愈性切除。我们假设同时进行肝切除术(PHx)和 PVL 会增强 FLR 的再生,并且这种效果与额外切除的程度有关。72 只 Lewis 大鼠被纳入 3 组:20%PVL+70%PHx;70%PVL+20%PHx;90%PVL。术后观察动物 1、2、3 和 7 天(n=6/时间点)。评估肝酶、尾状叶肝脏/体重比、BrdU 增殖指数(PI)、增殖细胞核抗原(PCNA)-mRNA 表达水平和自噬相关蛋白。与 90%PVL 相比,额外的 PHx 在观察期间诱导了更显著的肥大,这通过显著更高的 PI 和更高的 PCNA-mRNA 表达水平得到证实。同样,与单独的 PVL 相比,额外的 PHx 在 FLR 中诱导了更多的自噬。然而,这两种作用与额外切除的程度并没有明显的关系。与单独的 PVL 相比,额外的切除大大增强了肝再生和自噬。因此,我们得出结论,自噬可能在调节同时进行的 PVL+PHx 后肝细胞增殖和 FLR 的大小方面发挥关键作用。