安全な広範肝切除を目的とした門脈枝塞栓術の基礎的および臨床的研究

[临床研究]1)我们研制了三段门静脉栓塞术，为右肝或左肝三段切除做准备。右三段栓塞术为左内侧、右前、右后段栓塞，左三段栓塞术为左外侧、左内侧、右前段栓塞术。三段切除使肝三段切除安全可靠。2)设计门静脉加动脉栓塞术(双重栓塞术)，扩大功能储备不良患者广泛肝切除的适应证。这种新的介入治疗可以在未经栓塞的肝段产生相当大的肥大。3)应用多普勒超声检测栓塞后门脉血流速度。这项研究清楚地表明，根据门静脉血流速度增加的程度，可以预测未经栓塞的肝段在栓塞后的肥厚率。4)Angio-CT发现门静脉栓塞术后肝段肝动脉血流量即刻增加。[实验研究]1)采用门静脉结扎大鼠模型，探讨门静脉栓塞术后非栓塞区肝段肥大的机制。从聚合酶活性和线粒体功能的角度来看，门静脉栓塞术在非栓塞区诱导肝细胞增殖的方式类似于肝部分切除。2)采用门静脉分支结扎大鼠模型，研究了门静脉栓塞术后肝段萎缩的机制。这种萎缩是由肝细胞的凋亡引起的，而不是坏死。此外，我们还阐明了神经酰胺和/或鞘氨醇在细胞核内积聚的核鞘磷脂破裂可能会在体内诱导肝细胞的凋亡。

[Clinical Study] 1) We have developed trisegment portal vein embolization in preparation for right or left hepatic trisegmentectomy. In right trisegment embolization, the left medial, right anterior, and right posterior segments were embolized ; in left trisegment embolization, the left lateral, left medial, and right anterior segments were involved. Trisegment enibolization has made hepatic trisegmentectomy safe. 2) Portal plus arterial embolization (dual embolization) was devised, in order to expand the indication of extensive liver resection for patients with poor functional reserve. This new intervention can produce sizable hypertrophy in the non-embolized hepatic segments. 3) Portal blood flow velocity after embolization was estimated using Doppler ultrasound. This study clearly has demonstrated that the hypertrophy rate of non-embolized hepatic segments after embolization is predictable from the extent of the increase in portal blood flow velocity. 4) With Angio-CT, we have found an immediate increase in the hepatic artery blood flow in the embolized hepatic segments after portal vein embolization.[Experimental Study] 1) We have investigated the mechanism of hypertrophy in the non-embolized hepatic segments after portal vein embolization, using portal branch ligated rat model.. From the view point of polymerase activity and mitochondrial function, portal vein embolization induces hepatocyte proliferation in the non-embolized hepatic segments in a way similar to partial hepatectomy. 2) We have also studied the mechanism of atrophy in the embolized hepatic segments after portal vein embolization, using portal branch ligated rat model.. This atrophy results from, not necrosis, apoptosis of hepatocyte. In addition, we have elucidated that nuclear sphingomyelin breakdown with an accumulation of ceramide and/or sphingosine in nuclei may induce the apoptosis of hepatocyte in vivo.