Tihanyi Dora Krisztina, Szijarto Attila, Fulop Andras, Jiang Decan, Ernst Lisa, Meister Franziska Alexandra, Bleilevens Christian, Theissen Alexander, Nienhüser Henrik, Uluk Deniz, Lurje Georg, Arianeb Mehrabi, Tolba Rene H, Czigany Zoltan
Institute for Laboratory Animal Science and Experimental Surgery, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.
Department of Surgery, Transplantation and Gastroenterology, Hepato-Pancreatico-Biliary Surgical Research Center, Semmelweis University, Budapest, Hungary.
Cancer Rep (Hoboken). 2025 Jun;8(6):e70221. doi: 10.1002/cnr2.70221.
Associating liver partition and portal vein ligation (PVL) for staged hepatectomy (ALPPS) and selective PV embolization (PVE) are important clinical strategies in liver surgery. Even though it has been demonstrated that ALPPS induces a more rapid and expressed hypertrophy than PVL/PVE, this phenomenon is still not well understood.
In the present study, we aimed to characterize enhanced regeneration patterns in a rat model.
Male Wistar rats were used (n = 84; 220-250 g). Selective PVL and ALPPS were achieved using microsurgical techniques (RML-regenerating/LML-non-regenerating). Parameters of liver regeneration, microcirculation, hepatocyte morphology, hepatocellular injury, and activation status of certain protein kinases involved in liver regeneration were investigated.
Right median lobe (RMLs) in the ALPPS group exhibited a more significant and rapid hypertrophy compared to PVL (regeneration ratio, 1.669 ± 0.155 vs. 1.980 ± 0.189, p = 0.009, PVL vs. ALPPS). ALPPS led to a more prominent hepatocellular injury. Hypertrophy was associated with increased microcirculation of the RML and a prominent increase of hepatocellular size (300.43 ± 31.92 μm vs. 374.48 ± 58.34 μm, PVL vs. ALPPS) and morphology. There was an early pAkt/Akt activation after surgery which was significantly higher in ALPPS (5 ± 2 vs. 9.7 ± 3 RQ-fold-change, p = 0.0087, PVL vs. ALPPS).
Our results suggest that the enhanced regeneration in ALPPS is associated with characteristic changes in liver microcirculation, cell division, hepatocyte morphology, and activation of pAkt/Akt.
联合肝脏分隔与门静脉结扎分期肝切除术（ALPPS）和选择性门静脉栓塞术（PVE）是肝脏手术中的重要临床策略。尽管已经证明ALPPS比门静脉结扎/门静脉栓塞术能诱导更快速、更明显的肝脏肥大，但这种现象仍未得到充分理解。
在本研究中，我们旨在描述大鼠模型中增强的肝再生模式。
使用雄性Wistar大鼠（n = 84；体重220 - 250 g）。采用显微外科技术实现选择性门静脉结扎和ALPPS（RML - 再生叶/LML - 非再生叶）。研究肝再生、微循环、肝细胞形态、肝细胞损伤以及参与肝再生的某些蛋白激酶的激活状态等参数。
与门静脉结扎组相比，ALPPS组的右中叶（RML）表现出更显著、更快速的肥大（再生率，1.669 ± 0.155对1.980 ± 0.189，p = 0.009，门静脉结扎组对ALPPS组）。ALPPS导致更明显的肝细胞损伤。肥大与RML的微循环增加以及肝细胞大小（300.43 ± 31.92μm对374.48 ± 58.34μm，门静脉结扎组对ALPPS组）和形态的显著增加有关。术后早期pAkt/Akt激活，ALPPS组明显更高（5 ± 2对9.7 ± 3 RQ倍变化，p = 0.0087，门静脉结扎组对ALPPS组）。
我们的结果表明，ALPPS中增强的肝再生与肝脏微循环、细胞分裂、肝细胞形态以及pAkt/Akt激活的特征性变化有关。
