乳糖化多聚赖氨酸拉咪呋啶在慢性乙型病毒肝炎小鼠体内的肝靶向性研究  

The Study on Hepatic Targeting of Lactosaminated Multiple Poly Lysine Lamivudine in Mice

作　　者：孔令斌[1] 杨景玉 孙志[1] 

机构地区：[1]济宁医学院 [2]山东省消化系统疾病防治中心

出　　处：《济宁医学院学报》2008年第2期102-105,共4页Journal of Jining Medical University

基　　金：山东省教育厅资助项目(J05L16)

摘　　要：目的观察用乳糖化多聚赖氨酸化学修饰后的拉咪呋啶—乳糖化多聚赖氨酸拉咪呋啶在慢性乙型病毒性肝炎小鼠体内的分布情况,探讨Lac-PLL-LA的肝靶向性。方法将LA进行偶联合成后以放射性核素99mTc对偶联物Lac-PLL-LA及LA进行标记,分别通过单光子正电子发射断层显像(SPECT)和γ-放射免疫记数观察其在慢性乙型病毒性肝炎小鼠体内的分布情况。结果(1)慢性乙型病毒性肝炎小鼠注射99mTc标记的LA0.5h、2h及5h后肝脏部位显像模糊不清,各时间点99mTc标记的Lac-PLL-LA组小鼠肝脏部位显像剂的聚集程度均明显高于99mTc标记的LA组,两组显像剂的聚集程度差异有显著性(P<0.01)。(2)小鼠注射99mTc标记的Lac-PLL-LA后1到6h,肝脏/血液和肝脏/骨骼肌放射性比值分别从1.24、2.28上升到4.1、12.1,注射99mTc-LA后1到6h,肝脏/血液和肝脏/骨骼肌放射性比值分别从0.28、0.55上升到0.49、1.36。各时间点99mTc标记的Lac-PLL-LA肝脏/血液和肝脏/骨骼肌放射性比值均高于99mTc-LA,差别有非常显著性(P<0.01)。结论Lac-PLL-LA可在慢性乙型肝炎小鼠肝组织中特异性聚集,偶联后的拉咪呋啶能提高对肝脏组织的亲和力,乳糖化多聚赖氨酸能使LA获得较满意的肝靶向性,提高其抗乙肝病毒的作用。Objective To observe the distribution of lactosaminated multiple poly lysine lamivudine in mice. Investigating hepatic targeting of actosaminated multiple poly lysine lamivudine. Methods Used lactosaminated multiple poly lysine coupling lamivudine, this conjugates and lamivudine were labeled by radio nuclide （99m）Tc. After labeling, this conjugates and lamivudine were injected into mice. The distribution of conjugates and lamivudine in mice were observe by single photon emission computed of tomograph （SPECT） and γ- radio immunoassay. Results （1）After （99m）Tc- lactosaminated multiple poly lysine lamivudine and lamivudine injected,bio-distribution analysis was carried out at 0.5h、2h,5h by SPECT, the results showed that accumulation degree of （99m）Tc- lactosaminated multiple poly lysine lamivudine were significantly higher than that （99m）Tc- lamivudine in mice liver（ P 〈 0.01）. （2）After injected （99m）Tc- lactosaminated multiple poly lysine lamivudine and lamivudine 1h to 6h,the （99m）Tc-lactosaminated multiple poly lysine lamivudine concentration ratio of liver versus blood and skeletal muscle （1.24,2.28） were increased （4.1,12.1） respectly, the lamivudine concentration ratio of liver versus blood and skeletal muscle（0.28,0.55 were increased（0.49,1.36） respectly. The （99m）Tc- lactosaminated multiple poly lysine lamivudine concentration ratio at different time point were significantly higher than that of （99m）Tc- lamivudine. Conclusion The results suggested that hepatic targeting of lactosaminated multiple poly lysine lamivudine were significantly higher than that of lamivudine in mice.

关 键 词：拉咪呋啶 乳糖化多聚赖氨酸 偶联 肝靶向性 

分 类 号：R512.62[医药卫生—内科学] R223.11[医药卫生—临床医学]