Gao Yi, Mu Ning, Xu Xiao-Ping, Wang Yan
Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China.
World J Gastroenterol. 2005 Sep 21;11(35):5468-74. doi: 10.3748/wjg.v11.i35.5468.
To establish a highly reproducible animal model of acute liver failure (ALF), for assessing the effect of bioartificial liver support system (BALSS).
A two-phase complete liver devascularization procedure was performed in eight loco-hybrid pigs. Blood biochemical index and liver biopsy were studied every 2 h after surgery, and survival time was recorded. The BALSS constructed with high volume recirculating technique was a hollow fiber circulating system consisting of a hepatocyte reactor-hollow fiber module inoculated with microcarrier-adhering hepatocytes, and a double pump, heparinized, thermostabilized, micro-capsulized activated carbon-adsorbing plasmapheresis system. Twelve pigs undergoing two-phase surgery were randomized into: control group (perfused without hepatocytes, n = 6) and treatment group (perfused with hepatocytes, n = 6). Intergroup liver biochemical indexes, survival time, and liver pathological changes were analyzed at regular intervals.
Two-phase surgery was performed in all the experimental pigs, and there was no obvious difference between their biochemical indexes. After 3 h of phase II surgery, ammonia (Amm) increased to (269+/-37) micromol/L. After 5 h of the surgery, fibrinogen (Fib) decreased to (1.5+/-0.2) g/L. After 7 h of the surgery, ALT, AST, Tbil and PT were (7.6+/-1.8) nka/L, (40+/-5) nka/L, (55+/-8) micromol/L and (17.5+/-1.7) nka/L respectively. After 9 h of surgery, ALB and Cr were (27+/-4) g/L and (87+/-9) micromol/L. After 13 h of surgery, BUN was (3.5+/-0.9) micromol/L. All the above values were different from those determined before surgery. Survival time of pigs averaged 13.5+/-1.4 h. ALF pigs in the other group were treated with BALSS. The comparison analysis between the treated and control animals showed the changes of Tbil, PT, Alb, BUN, Cr, Fib, and Amm (P<0.01), but there was no change of ALT and AST. The survival time was statistically different (P<0.01), and there was no significant difference in histological changes.
The porcine ALF model established by two-phase devascularized surgery is valid and reproducible. The hollow fiber BALSS can meet the needs of life support and is effective in treating ALF.
建立一种高度可重复的急性肝衰竭（ALF）动物模型，用于评估生物人工肝支持系统（BALSS）的效果。
对8只本地杂交猪进行两阶段完全肝去血管化手术。术后每2小时研究血液生化指标和肝活检，并记录存活时间。采用大容量循环技术构建的BALSS是一种中空纤维循环系统，由接种微载体黏附肝细胞的肝细胞反应器 - 中空纤维模块和双泵、肝素化、热稳定、微囊化活性炭吸附血浆置换系统组成。12只接受两阶段手术的猪被随机分为：对照组（未灌注肝细胞，n = 6）和治疗组（灌注肝细胞，n = 6）。定期分析组间肝生化指标、存活时间和肝病理变化。
所有实验猪均进行了两阶段手术，其生化指标之间无明显差异。第二阶段手术后3小时，氨（Amm）升至（269±37）微摩尔/升。手术后5小时，纤维蛋白原（Fib）降至（1.5±0.2）克/升。手术后7小时，谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆红素（Tbil）和凝血酶原时间（PT）分别为（7.6±1.8）纳卡/升、（40±5）纳卡/升、（55±8）微摩尔/升和（17.5±1.7）纳卡/升。手术后9小时，白蛋白（ALB）和肌酐（Cr）分别为（27±4）克/升和（87±9）微摩尔/升。手术后13小时，尿素氮（BUN）为（3.5±0.9）微摩尔/升。上述所有值均与手术前测定的值不同。猪的平均存活时间为13.5±1.4小时。另一组的ALF猪用BALSS治疗。治疗组与对照组动物的比较分析显示Tbil、PT、Alb、BUN、Cr、Fib和Amm有变化（P<0.01），但ALT和AST无变化。存活时间有统计学差异（P<0.01），组织学变化无显著差异。
通过两阶段去血管化手术建立的猪ALF模型有效且可重复。中空纤维BALSS能够满足生命支持需求，对治疗ALF有效。
