脂质体-γ-干扰素DNA复合物肝内直接注射对大鼠肝纤维化的影响

Effects of direct injection of liposome-IFNγDNA complex into liver on rat liver fibrosis

目的 探讨脂质体 γ干扰素(γIFN )DNA复合物肝纤维化肝脏内直接注射后的表达及对肝纤维化的影响。方法 用阳离子脂质体包裹人γIFNDNA ,并直接注射入肝纤维化大鼠的肝实质内,3周后,用酶联免疫吸附试验(ELISA)法检测血内γIFN水平并评估肝纤维化程度变化。结果 肝内注射脂质体 γIFNDNA复合物的大鼠下腔静脉血中检测到了γIFN的表达(6.6±1.7)mg/L ,而对照组却未检出;行γIFN基因肝内注射的大鼠在基因转导前后,肝纤维化分期、Ⅳ型胶原染色及肝纤维化的Chevallier评分无明显改变(P >0 .0 5 ) ,且均显著轻于对照组(P <0 .0 5 )。结论 脂质体 DNA复合物进行肝实质内注射是一条肝纤维化肝内直接基因转导的有效途径。

Objective To investigate γ-IFN gene expression and its effects on liver fibrosis after direct injection of liposome-IFNγ DNA complex into fibrotic liver.Methods Human γ-IFN DNA was encapsulated with cationic liposome and then injected into the liver parenchyma of rats with liver fibrosis directly.Samples of blood and liver tissue were collected to evaluate the levels of γ-IFN and fibrotic degrees of liver 3 weeks after operation.Results The expression of γ-IFN gene was detected in inferior vena cava blood samples of rats with liposome-IFNγ DNA intrahepatic injection (6.6± 1.7) mg/L,but not detectab in rats of control groups.The fibrotic grade and IV collagen immunohistochemical staining and Chevallier scoring of tissues in rats with directly intrahepatic γ-IFN gene transduction had not obviously change after operation ( P > 0.05). But these showed significant difference in comparison with rats in control groups ( P < 0.05). Conclusion Intrahepatic injection with liposome-DNA complex might be an effective way to transduct foreign gene directly into fibrotic liver.Directly injecting foreign γ-IFN gene into liver could prevent or improve the liver fibrosis.