小体积肝移植损伤机制的实验观察

Experimental study on mechanism of graft injury of small-for-size liver transplantation in miniature pigs

目的探讨小体积移植肝损伤机制。方法采用肝周骨骼化的去神经解剖、肝切除和原位灌注建立巴马小型猪不同移植量肝移植模型。分为3组（n=5）：（1）A组：原位肝移植组；（2）B组：右半肝供肝肝部分移植组；（3）C组：右中叶和尾状叶供肝部分肝移植组。移植后观察动物7d存活率，动态监测门静脉压（PVP）、门静脉血流量（PBF）以及移植肝组织学病理改变。结果巴马小型猪不同移植量肝移植7d存活率分别为：A组100％（5／5）；B组100％（5／5）和C组20％（1／5）。C组移植肝复流后PVP立即升高，高峰达（28．6±2．07）mmHg，复流后1h单位肝组织PBF达（3．56±0．11）ml·min^-1·g^-1。C组移植肝组织病理改变严重，包括肝窦淤血、出血，肝细胞气球样变或肝细胞坏死，内皮细胞脱落，狄氏间隙增宽或消失以及明显的细胞凋亡。结论小体积肝移植中门静脉过度灌流和急性门静脉高压是移植肝的主要病因学机制。

Objective To elucidate the mechanisms of graft injury in small-for-size liver transplantation. Methods Animal models were established with skeletonized and denervated anatomic parahepatic dissection, hepatectomy and perfusion in situ. Chinese Bama miniature pigs were divided into three groups （ n = 5 ） ： Group A, liver transplantation ; Group B, partial liver transplantation with right hemi-liver graft and Group C, liver transplantation with right median and caudate lobe graft. Animals were followed for 7 days with regards to survival, dynamical portal venous pressure （PVP）, portal blood flow （PBF） and graft histopathological examination. Results Animal survivals were as follows ： Group A, 5/5, Group B, 5/5 and Group C, 1/5. PVP rose immediately after reperfusion. PVP in Group C peaked to 28.6 ± 2. 07 mm Hg. Portal blood flow （PBF） measured by CDFI showed that the index of PBF per gram liver tissue reached 3.56± 0. 11 ml.min^-1.g^-1 at the first hour post-reperfusion in Group C. Hepatic morphological examination showed that severe pathological changes occurred in small-for-size grafts, including sinusoidal congestion, hemorrhage, hepatocytic ballooning change or necrosis, endothelial cell detachment, Disse＇s space widening or vanishing and significant apoptosis. Conclusion Portal overperfusion and acute portal hypertension are the primary etiological mechanisms of graft injury in small-for-size liver transplantation.