硫代寡核苷酸在小鼠体内脏器生物分布研究

Organic biodistribution study of phosphorothioated oligodeoxynucleotides in mice

探讨硫代寡核甘酸 (PSODN)在小鼠体内脏器生物分布。合成互补于乙型肝炎病毒pre -c/c基因的PSODN :5’ -CATGCCCCAAAGCCAC - 3’ ,用T4多核苷酸激酶进行 5’端3 2 P标记后 ,小鼠尾静脉给药 ,分别于不同时间点处死小鼠并取各脏器及血液 ,液相闪烁计数仪测放射性计数。PSODN在血中很快清除 ,半衰期约 1～ 2分钟 ;在所有脏器中 ,肝摄取量最高 ,30分时脏器放射性大小依次为肝 >肾 >肺 >心 >脾 >脑。随后 ,肝脏放射性逐渐降低 ,2 4小时后是所给药物的 2 93%。肝脏作为反义治疗的靶器官有现实意义 ,建议PSODN给药间隔为 2

To investigate the organic biodistribution of phosphorothioated oligodeoxynucleotides (PSODN) in mice.PSODN:(5'-CATGCCCCAAAGCCAC-3')targeted to HBVpre-C/C region was synthesized.The PSODN was radiolabeled with 32P at the 5' terminus with T4-polynucleotide Kinase and was injected via the lateral tail vein of mice.Samples of blood were collected and various organs were removed respectively at various time points.Total radioactivity in each sample was measured in a liquid scintillation counter.Plasmal levels of PSODN were rapidly depleted,with a half-life of approximately 1～2 minutes.The liver retained the highest amount of PSODN;At the time point of 30 minute,the degree of redioactivity in organs was as following:Liver>kidney>lung>heart>spleen>brain.PSODN in liver decreased gradually,which was about 2.93% of injected dose at 24 hour.Liver was the satisfied organ for antisense therapy.And the recommended drug injection interval was 24hours.