急性肝衰竭是一种进展迅速，以黄疸、腹水、明显意识和凝血功能障碍为表现的临床症候群。人工肝降低胆红素等代谢毒素，是治疗急性肝衰竭的主要方法。传统人工肝胆红素吸附性能有限，生物安全性差，临床应用效果有待提升。本课题组前期制备的赖氨酸固定化甲壳素/碳纳米管复合微球具有明确的生物安全性和胆红素物理吸附的性能，然而其对胆红素代谢关键酶UGT1A1的影响不佳。我们推测：人工肝中载有上调UGT1A1的腺相关病毒可通过静电作用接合于复合微球表面，从而增加体外肝细胞对胆红素的代谢能力。本项目借助zeta电位测试与电子显微镜等验证该复合微球的制备效率，选用大鼠全血灌流和肝细胞培养模型，阐明该复合微球对UGT1A1信号通路的调控效果。通过猪人工肝应用模型和高通量测序技术，进一步明确该复合微球的生物安全性与有效性，并探究其对体内生理过程的影响，为相关生物活性材料在人工肝的应用提供新思路。

Acute liver failure (ALF) is a rapidly progressing clinical syndrome which is characterized by jaundice, ascites, apparent disorders of consciousness and coagulation. Artificial liver support system (ALSS) is the main treatment for ALF by reducing metabolic toxins such as bilirubin. Due to the poor bilirubin adsorption performance and poor biocompatibility of the traditional ALSS, the clinical application effect needs to be improved. Our group found that lysine-immobilized chitin/carbon nanotubes microspheres have good biocompatibility and the capacity which could promote bilirubin adsorption and hepatocyte growth. However, it has little effect on UDP-glucuronyltransferase1A1 (UGT1A1), a key enzyme of bilirubin metabolism. We hypothesized that the adeno-associated virus(AAV), which could up-regulate the expression of UGT1A1, could be joined to the surface of composite microspheres by electrostatic interaction. The composite microspheres could ameliorate physical adsorption performance of bilirubin in vitro. This project aims to test preparation efficiency of the composite microspheres by zeta potential, electron microscope and so on. Rat blood perfusion and hepatocyte culture models are used to clarify the regulation effect of the composite microspheres on UGT1A1 signaling pathway. Biocompatibility and effectiveness of composite microspheres are measured by applying ALSS on pigs and high-throughput sequencing, thereby providing new ideas for the application of bioactive materials.