永生化肝细胞微囊化移植治疗大鼠肝豆状核变性

目的：观察微囊化 HepG2 细胞腹腔移植治疗肝豆状核变性（HLD）模型大鼠的疗效。方法：3 月龄 Wistar 雄性大鼠 120 只随机分为HLD模型组、裸 HepG2 细胞腹腔移植组和微囊化 HepG2 细胞移植组，采用铜负荷饮食法制作大鼠 HLD 模型。根据移植后标本采集时间分设 3 d、7 d、14 d、21 d、28 d 5个时间点，每时间点 8 只大鼠; 另取 8 只大鼠设为空白对照组。测定血清ALT、AST、白蛋白水平及血清铜、肝铜含量。结果：模型组、裸 HepG2 细胞腹腔移植组、微囊化 HepG2 细胞移植组大鼠各时间点 ALT、AST、血清铜、肝铜水平均较空白对照组升高（P<0.05），合成白蛋白水平明显下降（除外微囊化 HepG2 细胞移植组28 d与空白组比较差异无统计学意义）。在大部分时间点裸HepG2细胞腹腔移植组、微囊化HepG2细胞移植组大鼠 ALT、AST、血清铜、肝铜值水平较模型组下降（P<0.05），而白蛋白水平则较模型组增加（P<0.05）。7~14 d后微囊化 HepG2 细胞移植组大鼠 ALT、AST、血清铜、肝铜水平较裸 HepG2 细胞腹腔移植组明显下降（P<0.05），而白蛋白则于 14 d后高于裸 HepG2细胞腹腔移植组。结论：HepG2 细胞微囊化腹腔移植可明显减轻 HLD 大鼠的肝损害，减少肝铜沉积，加速血清铜的代谢，可成为一种细胞移植治疗 HLD 的新方法。［中国当代儿科杂志，2010，12(12)：959-962］

Efficacy of microencapsulated HepG2 cells transplantation in rats with hepatolenticular degeneration

Objective To evaluate the efficacy of intraperitoneal transplantation of microencapsulated HepG2 cells in rats with hepatolenticular degeneration(HLD).Methods HLD was induced by copper-overloaded diet with forage containing 1 g/kg copper sulfate and water with 0.185% copper sulfate for 12 weeks in rats.One hundred and twenty three-month-old male Wistar rats were randomly intraperitoneal injected with normal saline(NS),microencapsulated HepG2 cells or non-microencapsulated HepG2 cells 9 weeks after copper-overloaded diet.Blood or liver samples were obtained at five time points:3,7,14,21 and 28 days after transplantation(n=8).The other 8 rats receiving normal diet were used as the control group.Serum levels of ALT,AST,albumin and Cu and liver Cu contents were measured.Results Serum ALT,AST and Cu levels and liver Cu contents in the NS-treated HLD,microencapsulated HepG2 cells and non-microencapsulated HepG2 cells transplantation groups increased significantly at all time points,in contrast,serum albumin levels decreased significantly in the NS-treated HLD and non-microencapsulated HepG2 cells transplantation groups compared with those in the control group at all time points(P<0.05),but serum albumin levels in the microencapsulated HepG2 cells transplantation restored to the level of the control group 28 days after transplantation.Serum ALT,AST and Cu levels and liver Cu contents in the microencapsulated HepG2 cells and non-microencapsulated HepG2 cells transplantation groups were significantly lower,in contrast,albumin levels were higher than those in the NS-treated HLD group on almost time points(P<0.05).Serum levels of ALT,AST and Cu and liver Cu contents in the microencapsulated HepG2 cells transplantation group decreased 7 or 14 days after transplantation,while serum albumin levels increased significantly 14 days after transplantation compared with those in the non-microencapsulated HepG2 cells transplantation group(P<0.05).Conclusions Intraperitoneal transplantation of microencapsulated HepG2 cells can relieve hepatic damage,reduce serum and liver Cu levels,and improve copper metabolism,therefore it is promising for the treatment of HLD.