中文摘要：

目的探讨急性肝衰竭（AIJF）大鼠载肝细胞生长因子（HGF）的聚乳酸-氧-羧甲基壳聚糖（PLA—O—CMC）纳米粒子肝细胞移植后有丝分裂指数和Ki-67抗原的表达变化及意义。方法D-氨基半乳糖腹腔内注射制作大鼠ALF模型，48h后分别将Ⅰ型胶原（Ⅰ组）、PLA—O—CMC纳米粒子（Ⅱ、Ⅳ组）、载HGF的PLA—O—CMC纳米粒子（Ⅲ组）培养的大鼠肝细胞（均为5×10^7个，5ml）移植到ALF大鼠腹腔内。以每日静脉注射HGF10μg／kg×7d（1V组）、5ml RPMI 1640腹腔内注射（V组）作为对照。观察其14d存活率、血清及肝组织HGF浓度、肝组织病理及有丝分裂指数（MI）、Ki-67变化。结果移植后14dⅠ～Ⅴ组ALF大鼠的存活率分别为50．00％、68．75％、81．25％、75．00％、18．75％。各纳米移植组高于Ⅴ组。Ⅲ组3d时肝组织HGF浓度最高，平均为5882．91μg／L。1I组肝组织结构恢复更快，5d时平均MI10．20％0、7d时Ki-67平均标记指数16．8‰，均高于Ⅴ组。结论应用载HGF的PLA-O-CMC纳米粒子培养的大鼠肝细胞腹腔内移植治疗ALF大鼠能促进肝再生相关抗原表达。

英文摘要：

Objective To evaluate the change and significance of Ki-67 antigen expression follow- ing hepatocyte transplantation using hepatocyte growth factor （HGF） loaded polylactic acid-O-carboxymeth-ylchitosan （PLA-O-CMC） nanoparticles in rats with acute liver failure （ALF）. Methods ALF models of rats were established by D-galactosamine intraperitoneal injection. Rat hepatocytes type Ⅰ collagen suspension （group Ⅰ ）, rat hepatocytes co-cultured with PLA-O-CMC nanoparticles （groups Ⅱ , Ⅳ ） and rat hepatocytes co-cultured with HGF loaded PLA-O-CMC nanoparticles （group Ⅲ ） （5 × 10^7 cells each group, 5 ml） were transplanted into the abdominal cavity of SD rats at 48 h after D-Gal injection. Intravenous injection of HGF （10μg/kg for 7 days） （group Ⅳ ） and RPMI 1640 injection （group V ） were used as the negative groups. The 14th-day survival rate of rats, pathological change and mitotic index of liver, Ki-67 antigen labeling index of ALF rat livers were observed. Results The 14th-day survival rate in groups Ⅰ -Ⅴ was 50. 00%, 68.75%, 81.25%, 75.00%, 18.75%, and that in nano-transplanted groups was higher than in group V. At the 3rd day, the concentration of HGF in liver tissue of group Ⅲ, average 5882.91 μg/L was the highest. The hepatic lobules structure in group Ⅲ recovered faster. The average mitotic index in group Ⅲ at the 5th day was 10. 20%0 and the average Ki-67 labeling index at the 7th day was 16. 8‰, which were all higher than in group V. Conclusion Intraperitoneal transplantation of HGF loaded PLA-O-CMC nanoparticle-attached hepatocytes for treatment of ALF can promote the liver regenerationassociated antigen expression.