中文摘要：

目的经胆道分支逆行导入非病毒载体基因复合物，观察目的基因在正常及急性损害大鼠局部肝脏的定量定位表达。方法运用D-氨基半乳糖制作大鼠急性肝损害模型；非病毒载体基因复合物polylysine-molossin／DNA／fusogenic经胆管分支分别将包含萤火虫荧光素基因质粒pGL3及包含大肠埃希氏菌β半乳糖苷酶基因质粒CMVβ逆行导人大鼠局部肝脏，定量检测荧光素酶和定位检测β半乳糖苷酶在肝脏的表达。结果荧光素酶基因在正常大鼠肝脏极少表达，在急性肝脏损害恢复期（造模后第4—7天）表达水平显著增加（P〈0．05），在造模后第9天表达水平与正常组无显著差别。大肠埃希氏菌β半乳糖苷酶定位检测见急性肝损害大鼠肝脏内显著表达，正常大鼠肝脏几乎无表达，其中可见较多肝细胞表达。基因导入可引起血清ALT、AST水平升高，血清白蛋白水平略下降，但基因表达与肝功能酶生化指标水平及变化无明显相关。组织学改变不显著。结论非病毒载体基因复合物导入急性损害肝脏局部能获得较好表达，且无明显加重肝脏损害，该项方法为肝脏基因治疗的实验研究提供了良好的技术平台。

英文摘要：

Objective To evaluate the efficacy of gene delivery to the right lateral lobe of liver via a branch of the bile duct. Methods Twenty LEW rats underwent intraperitoneal injection of D-galactosamine to establish acute liver damage models and were randomly divided into 5 groups to undergo ligation of the common bile duct and left bile duct 4, 5, 6, or 7 days after the acute liver damage. Non-viral vector gene compound, polylysine-molossin/pGL3 containing firefly luciferin gene or CMV[5 containing β-galactosidase of Escherichia coli/fusogenic） was injected in to the right lateral lobes 2 and 3 via the branch of right bile duct. Four rats without injection of D-galactosamine but undergoing injection of polylysine-molossin/pGL3 or CMVβ/fusogenic were used as normal controls. Twenty-four hours after the regional gene delivery the rats were killed. The expressions of luciferin and β-galactosidase in different lobes were detected. Pathological examination of liver was conducted. Results All rats survived after the operation. The expression levels of luciferin in the liver on the days 4, 5, and 6 were all significantly higher than that of the normal control rats （ all P 〈 0.05 ）. The expression levels of luciferin in the liver on the day 7 was the highest compared with the normal control rats （P =0.01 ）. However, the level of luciferin in the liver on the day 9 was lower and not significantly different from that of the normal rats （ P 〉 0.05 ）. Scattered distribution of β-galactosidase was seen in the lobe 2 of the rats with acute liver damage. The levels of alanine transaminase and aspartate aminotransferase were slightly increased and the albumin level was slightly decreased in the rats with acute liver damage on the days 4 and 7, however, these biochemical indexes were not significantly correlated with the gene expression. There was no obvious histological difference between the lobes 2 and 3 and lobe 1. Conclusion Gene delivery with peptide/DNA complexes shows a good expression in the acute damage