Xu Qingxiang, Yu Decai, Qiu Yudong, Zhang Heyuan, Ding Yitao
Hepatobiliary Surgery Department, Affiliated Drum Tower Hospital, Hepatobiliary Institute, Medical College of Nanjing University, Nanjing, Peoples' Republic of China.
Ann Clin Lab Sci. 2003 Summer;33(3):306-12.
The goal of this study was to determine whether a new internal bioartificial liver utilizing porcine hepatocytes can perform detoxification and other metabolic functions. Such a system might aid in treating patients with moderate to severe liver failure and prolong patient survival until a matching organ is found for transplantation. Porcine hepatocytes were attached to a microcarrier and an internal artificial liver was constructed by perfusing the hepatocytes into a polysulfon hollow fiber. The 4 experimental groups were: (a) control group, (b) microcarrier group, (c) hollow fiber group, and (d) internal bioartificial liver group. Viability of hepatocytes, alanine aminotransferase (ALT) and lactate dehydrogenase (LD) activities in the medium, urea production, diazepam transformation, protein synthesis, and glucose-6-phosphatase activity of cells were monitored during a 7-day culture period. Viability of porcine hepatocytes in the internal bioartificial liver group was maintained at >80% during the culture period, and alanine aminotransferase and lactate dehydrogenase activities did not fluctuate significantly. These enzyme activities were significantly lower in the internal bioartificial liver group than in the control or microcarrier groups. Urea production, diazepam transformation, [3H]-leucine incorporation, and glucose-6-phosphatase activity were significantly higher in the internal bioartificial liver group than in the control and hollow fiber groups. These results show that the new internal bioartificial liver produces small amounts of ALT and LD and exhibits detoxification and protein synthetic functions.
本研究的目的是确定一种利用猪肝细胞的新型体内生物人工肝是否能够执行解毒及其他代谢功能。这样的系统可能有助于治疗中重度肝功能衰竭患者,并延长患者生存期,直至找到匹配的器官进行移植。将猪肝细胞附着于微载体上,并通过将肝细胞灌注到聚砜中空纤维中来构建体内人工肝。4个实验组分别为:(a)对照组,(b)微载体组,(c)中空纤维组,以及(d)体内生物人工肝组。在为期7天的培养期内,监测肝细胞活力、培养基中的丙氨酸转氨酶(ALT)和乳酸脱氢酶(LD)活性、尿素生成、地西泮转化、蛋白质合成以及细胞的葡萄糖-6-磷酸酶活性。体内生物人工肝组猪肝细胞的活力在培养期内维持在>80%,丙氨酸转氨酶和乳酸脱氢酶活性无明显波动。体内生物人工肝组的这些酶活性显著低于对照组或微载体组。体内生物人工肝组的尿素生成、地西泮转化、[3H]-亮氨酸掺入以及葡萄糖-6-磷酸酶活性显著高于对照组和中空纤维组。这些结果表明,新型体内生物人工肝产生少量的ALT和LD,并具有解毒和蛋白质合成功能。