State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infection Diseases, Zhejiang University, Hangzhou, China.
Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China.
J Hepatol. 2015 Aug;63(2):378-87. doi: 10.1016/j.jhep.2015.03.018. Epub 2015 Mar 24.
BACKGROUND & AIMS: Extracorporeal blood purification systems for supportive therapy of liver failure are widely used. We developed a novel blood purification system, named Li's artificial liver system (Li-ALS), which couples low-volume plasma exchange (low-volume PE) with plasma filtration adsorption (PFA). This study aims to evaluate the efficacy of our novel system in pigs with acute liver failure (ALF).
Thirty-two pigs were infused with D-galactosamine (1.3g/kg) to induce ALF. All animals were equally and randomly divided into four groups: the ALF control group received intensive care, the PFA group underwent five hour plasma recycling filtration and adsorption purification, the low-volume PE group received one hour low-volume PE, and the Li-ALS group underwent one hour low-volume PE, followed by five hour PFA. Intervention was initiated 36hours after drug administration. The efficacy of each treatment was assessed by survival time and improvement in hematological, biochemical, and immunohistological parameters.
Pigs in the Li-ALS group survived longer than those in the other groups (p<0.001, ALF control: 60±2h; PFA group: 74±2h; low-volume PE group: 75±2h; and Li-ALS group: 90±3h). Liver enzyme, bilirubin, bile acid and blood ammonia levels were decreased significantly after Li-ALS treatment, and increases in inflammatory cytokines were ameliorated. A higher hepatocyte regeneration index was also observed in the Li-ALS group.
Our novel Li-ALS could expedite liver regeneration and improve survival time; hence, it could be promising for treating ALF.
体外血液净化系统广泛应用于肝功能衰竭的支持性治疗。我们开发了一种新型血液净化系统,命名为李氏人工肝系统(Li-ALS),它将小容量血浆置换(小容量 PE)与血浆滤过吸附(PFA)相结合。本研究旨在评估该新型系统在急性肝衰竭(ALF)猪模型中的疗效。
32 头猪通过给予 D-半乳糖胺(1.3g/kg)诱导 ALF。所有动物等分为四组:ALF 对照组接受强化护理,PFA 组进行五小时血浆再循环过滤和吸附净化,小容量 PE 组进行一小时小容量 PE,Li-ALS 组进行一小时小容量 PE,随后进行五小时 PFA。干预在给药后 36 小时开始。通过生存时间和血液学、生化学和免疫组织化学参数的改善来评估每种治疗的疗效。
Li-ALS 组的猪比其他组的猪存活时间更长(p<0.001,ALF 对照组:60±2h;PFA 组:74±2h;小容量 PE 组:75±2h;Li-ALS 组:90±3h)。Li-ALS 治疗后,肝酶、胆红素、胆汁酸和血氨水平显著降低,炎症细胞因子水平升高得到改善。Li-ALS 组的肝细胞再生指数也更高。
我们的新型 Li-ALS 可以加速肝脏再生并延长生存时间,因此有望用于治疗 ALF。