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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 glycosylated polylysine on liver targeting and localization of the introduced gene, and to observe the effect of intravenous route and intraperitoneal injection on liver targeting of the introduced gene. Methods Eukaryotic expression plasmids were respectively conjugated with liposomes and glycated poly-L-lysine, and were respectively injected into tail vein and intraperitoneal injection in rats. In situ hybridization and immunohistochemistry were used to observe the expression of target gene in liver And other organs in the distribution of expression. Results The plasmid DNAs embedded in liposomes or glycosylated polylysine were obviously expressed in vivo 24 hours after treatment, and gradually decreased after one week and still expressed at the third week. All of them had liver as the main distribution organ, The distribution of polylysine-coupled receptors in the liver was higher than that of the liposomes, and that of the other organs was lower than that of the liposomes. The transfection of the plasmid DNA The distribution in the liver is higher than that of the trans-celiac route. Conclusion Glycated poly-L-lysine is more effective than liposomes in targeting the liver of plasmid DNA. The hepatic targeting effect of transglycosylated poly-lysine is better than that of trans-abdominal route.