原位辅助性部分肝移植治疗门静脉高压症的实验研究

Preliminary experimental study on treatment of portal hypertension with auxiliary partial orthotopic liver transplantation

目的 在原位辅助性部分肝移植(APOLT)动物模型基础上,观察其对猪肝硬化门静脉高压症的初步治疗效果。方法 采用结扎胆总管的方法复制猪胆汁性肝硬化动物模型,6只健康良种幼猪作为供体组,6只肝硬化模型猪为受体组,肝移植采用APOLT术。术中观察血流动力学和生化指标;术前、术后当天及7 d观察门静脉压力、血胆红素及肝功能,同时用彩色多普勒超声检查门静脉最大流速及流量。结果 胆总管结扎8周后见肝脏假小叶形成,小叶周围结缔组织增生明显,有胆栓及胆泥沉积,证实胆汁性肝硬化模型成功。6只猪APOLT术后5只存活。术后7 d动物活杀病理检查见移植肝形态、色泽正常,各吻合口无扭曲、漏血和血栓形成;移植肝部分肝小叶结构紊乱,肝细胞萎缩或消失,肝小叶内大量淋巴细胞和浆细胞浸润,中央静脉周围肝小叶细胞浊肿,可见淋巴细胞浸润;受体肝无明显变性及坏死。术后7 d存活猪经彩色多普勒超声检察发现,移植肝门静脉血流比宿主肝门静脉血流增多,回流通畅,移植肝功能良好。血总胆红素、丙氨酸转氨酶及天冬氨酸转氨酶等肝功能指标明显好转,术后7 d门静脉压力与术前相比显著降低。结论 APOLT术对门静脉高压症有一定的治疗作用,是一种较有希望的治疗肝硬化门静脉高压的新方法。

Objective To evaluate the therapeutic efficacy of auxiliary partial orthotopic liver transplantation(APOLT) on portal hypertension in liver cirrhosis with amelioration of portal vein congestion, changes in portal vein pressure and status of the graft. Methods The recipients were percine model of biliary cirrhosis reproduced by ligation of the common bile duct. During transplantation, arterial blood pressure, central venous pressure were recorded. Buffer base, standard bicarbonate and pH of arterial blood samples were determined and analyzed in order to assess the impact of operation on the animals. The hemodynamics were also monitored. Color Doppler ultrasonagraphic examination was performed on recipients before operation, intraoperation and 7 days after operation, respectively. Portal vein pressure, blood bilirubin and variables of liver function were measured by using an autoanalyzer. Wedge biopsy specimens of each pig were obtained, stained with hematoxylin - eosin, and examined. Analysis of variance was performed. Otherwise nonparametrical tests were used. Results Eight weeks after ligation of the common bile duct, biliary cirrhosis was reproduced in all the pigs, and histopathological examination of the liver specimen showed a large number of pseudo - lobulations. In 6 pigs with hepatic cirrhosis liver transplantation was done. Five of the 6 (83. 3%) animals survived for 7 days. One recipient died because of unsuccessful operation, the others showed stable hemodynamics during the operation. Seven days after transplantation, the blood flow of the two liver portal veins was observed by the use of color Doppler ultrasonography. It was found that the blood flow in the donor portal vein was much richer than that of native portal vein. The venous outflow of the graft was ample and smooth, and no thrombosis of the hepatic vein or portal vein was found. The variables, including alanine aminotransferase, aspartate aminotransferase, bilirubin and total bilirubin, were significantly improved 7 days after operation compared with pre-operative data. Portal pressure was found to be (20. 76±2. 42)cm H2O(1 cm H2O=0.098 kPa), (17. 62±2.33)cm H2O and (14. 72±2. 25)cm H2O before the operation, during the operation, and 7 days after operation, respectively, and the difference was statistically significant (P<0.01 ). On the 7 days after transplantation, histopathological examination revealed evidence of damage with mild steatosis and sporadic necrotic hepatocytes and focal hepatic lobular degeneration in the graft, especially in the area around the central vein. Conclusion APOLT is a hopeful option for the treatment of portal hypertension. This procedure can provide not only some improvement of the liver function but also decrease the pressure of portal vein.