AP-2调控网格蛋白介导壳聚糖-DNA纳米粒子促肝再生的效应及机制研究

Although normal liver usually owns strong regeneration capacity, the inadequate of remnant liver regeneration is the main factor of the liver function failure post hepatectomy. Previous study showed that chitosan-DNA nanoparticles have great advantages in transporting drugs by retrograde injection of bile duct (RII) into hepatocytes compared with the pathways including nanofiber scaffolds、portal vein.or peripheral vein injection. However, the mechanism of transmembrane transport of nanoparticles from bile duct into hepatocytes is not clear. Clathrin-mediated endocytosis is the main pathway for the vast majority of particles, and it has been confirmed by a couple of experiments. Based on the current results, the hypothesis is proposed that chitosan-DNA nanoparticles, which loaded the growth factors is possible mediated by AP-2 through clathrin-mediated endocytosis to regulates nanoparticles transmembrane transport into hepatocytes during RII pathway, thus growth factors were released and play a critical role in promoting regeneration. The transport mechanism of chitosan-DNA nanoparticles transmembrane from bile duct transport into hepatocytes will be explored during RII.

正常肝组织虽具有较强的再生能力，但肝切除后残余肝组织再生不足是导致肝衰竭的主要原因。前期研究表明壳聚糖-DNA纳米粒子经逆行胆管内注射（RII）向肝实质细胞输送给药与纳米纤维膜给药、门静脉或外周静脉给药相比具有多方面优势。但壳聚糖-DNA纳米粒子进入肝细胞的具体跨膜转运方式及作用机制的研究尚属空白。经网格蛋白介导的细胞内吞作用是纳米粒子进入细胞的主要作用方式，并已得到证实。基于前期结果和目前的研究现状，携带生长因子的壳聚糖-DNA纳米粒子经RII后，通过衔接蛋白-2（AP-2）介导网格蛋白调控纳米粒子跨膜转运，表达生长因子基因，从而发挥促再生效应。我们将通过体内外实验对上述机制进行研究，探讨壳聚糖-DNA纳米粒子经RII给药的作用机制。对将来利用RII途径给予壳聚糖-DNA纳米粒子提高肝再生效率提供实验依据和理论基础。

正常肝组织虽具有较强的再生能力，但肝切除后残余肝组织再生不足是导致肝衰竭的主要原因。前期研究表明壳聚糖-DNA纳米粒子经逆行胆管内注射（RII）向肝实质细胞输送给药与纳米纤维膜给药、门静脉或外周静脉给药相比具有多方面优势。但壳聚糖-DNA纳米粒子进入肝细胞的具体跨膜转运方式及作用机制的研究尚属空白。经网格蛋白介导的细胞内吞作用是纳米粒子进入细胞的主要作用方式，并已得到证实。基于前期结果和目前的研究现状，携带生长因子的壳聚糖-DNA纳米粒子经RII后，通过衔接蛋白-2（AP-2）介导网格蛋白调控纳米粒子跨膜转运，表达生长因子基因，从而发挥促再生效应。我们将通过体内外实验对上述机制进行研究，探讨壳聚糖-DNA纳米粒子经RII给药的作用机制。对将来利用RII途径给予壳聚糖-DNA纳米粒子提高肝再生效率提供实验依据和理论基础。