体外生物人工肝支持作用的实验研究

Liver support effect of experimental extracorporeal bioartificial liver

构建理想的体外生物人工肝支技系统（ＥＢＬＳＳ），探讨其对暴发性肝衰竭（ＦＨＦ）的支持作用。方法用经体外两步灌流祛分离，限制贴壁技术球形聚集混合培养的人肝细胞一肝非实质细胞与中空纤维型生物反应器及由血液透析仪改装的辅助循环装置共同构建的ＥＢＬＳＳ，对门腔静脉分流加人肝血液阻断法建立的ＦＨＦ模型犬进行人工肝支持实验。结果在平均约 １０８肝细胞一肝非实质细胞ＥＢＬＳＳ的支持下，治疗组犬存活时间较无细胞空白循环对照组延长近一倍［分别为（５．８±０．５）小时和（１０．７±１．１）小时］，其血压、心率、心电图等改变较迟缓。在ＥＢＬＳＳ循环５小时内，支持组血氨、乳酸升高亦无对照组明显，两组犬３小时和５小时的血氨、乳酸变化有显著差异（Ｐ＜０．０１）。所用细胞均保持较好的活力和贴壁能力．结论所建ＥＢＬＳＳ已发挥出培养肝细胞的生物台成与解毒代谢作用，能够部分代偿ＦＨＦ的肝脏功能，将有可能为临床ＦＨＦ及重型肝炎患者提供有效的人工肝支持和治疗。

Objective To establish an extracorporeal bioartificial liver support system (EBLSS) and'study its support effect for fulminant hepatic failure (FHF). Methods The EBLSS consists of three parts:human liver cells (hepatocytes, nonparenchymal hepatocytes) isolated and cultured by extracorporeal twostege perfusion and spheroidal aggregates methods respectiyely, hollow fiber bioreactor, and supplementary circulation unit, which was employed to support the FHF model dogs. Results Compared withthe control dogs treated with EBLSS but without liver Cells, the survival time of artificial liver supportdogs was significantly prolonged, the changes of blood pressure, heart rate and ECG were slower, and theserum ammonia and lactate lavels were significantly lower at the 3 and 5 hr. In addition, a good viabilityof human liver cells was noted after 5 hr experiment. Conclusion This EBLSS has played the metabolicrole of cultured heman hepatocytes, is capable of compensating the function of the liver, and mightprovide effective artificial liver support and therapy for patients with FHF or severe hepatitis.