不同载体和不同导入途径对外源基因肝脏靶向导入效果的比较

Comparative studies of different carriers and introducing routes on the effects of liver targeted uptake of exogenousgene

目的比较脂质体和糖化多聚赖氨酸对所携带的导入基因肝脏靶向定位效果的影响，同时观察静脉途径和腹腔对导入基因肝脏靶向定位效果的影响。方法将真核细胞表达质粒分别与脂质体和糖化多聚赖氨酸偶联，分别经尾静脉注射和腹腔注射导入大鼠体内，运用原位杂交和免疫组织化学的方法观察目的基因在肝脏和其他脏器中的分布表达。结果经脂质体或糖化多聚赖氨酸包埋的质粒 ＤＮＡ导入体内 ２４ ｈ后均见明显表达，一周后逐渐下降，三周时仍有表达；均以肝脏为主要分布器官，但用糖化多聚赖氨酸偶联者在肝脏中的分布表达高于使用脂质体的包埋，在其他脏器中的分布表达低于使用脂质体的包埋；经静脉途径导入者，质粒ＤＮＡ在肝脏中的分布表达高于经腹腔途径导入者。结论糖化多聚赖氨酸对质粒ＤＮＡ的肝脏靶向定位效果优于脂质体；经静脉途径导入者其肝脏的靶向定位效果优于经腹腔途径的导入。

Objective To compare the effects of liposomes and glyco-poly-L-lysine (G-PLL) on target uptake and gene expression of the liver, and to observe the effects of intravenous route and intraperitoneal route on target uptake and gene expression of the liver. Methods After encapsulated by liposomes or galactose-terminal glyco-poly-L-lysine, the plasmid which can be expressed in eukaryotic cells was transferred into rat's body by intravenous injection and peritoneal injection respectively, then observed the results in different time by in situ hybridization and immunohistochemistry. Results The expression of the plasmid encapsulated by liposomes or G-PLL was obvious after transferred in vivo 24 h later, and one week later the expression began to decrease, but still could be found three weeks later. Both liposomes and G-PLL made the liver as the major distribution tissue. In the liver, the distribution and expression of the plasmid encapsulated by G-PLL were higher than those encapsulated by liposomes; in other tissues, however, the distribution and expression of the plasmid encapsulated by G-PLL were lower than those by liposomes. The distribution and expression of the plasmid transferred via intravenous route were higher in the liver than that transferred via intraperitoneal route. Conclusion The effect of G-PLL on liver target uptake and expression is better than that of liposome; The effect of intravenous route on liver target uptake and expression of the plasmid binding to G-PLL is better than that of peritoneal route.