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目的 :研究神经生长因子 (nervegrowthfactor,简称NGF)在小鼠体内的药代动力学。 方法 :12 5I NGF用氯胺T法制备经静注和肌注两种途径 ,血浆中NGF的浓度采用同位素示踪结合三氯醋酸 (TCA)沉淀法或SDS PAGE电泳法 ,测定小鼠血浆NGF的浓度。结果 :静注12 5I NGF 2 5 μg·kg-1,电泳法测得消除半衰期t1/ 2 β为 2 .2 2 3h ,酸沉法为 2 .2 6 4h。肌注12 5I NGF75 ,2 5 ,1 0 μg·kg-1,电泳法测得消除半衰期t1/ 2 β分别为 2 .1 4 0 ,2 .331 ,3.1 73h ,酸沉法测得消除半衰期t1/ 2 β分别为 2 .480 ,2 .5 5 2 ,2 .6 42h ,达峰时间tmax为 0 .5 83h。电泳法和酸沉法测得12 5I NGF平均血浆清除率 (Cl)分别为 0 .32 1和 0 .332L·h-1·kg-1,表观分布容积 (Vd)为 1 .2 5 9和 1 .31 5L·kg-1,体内平均滞留时间 (MRT)为 3.5 92和 3.5 39h。结论 :NGF在体内消除半衰期较短。本研究为今后的临床应用提供了必要的参考资料。
Objective: To study the pharmacokinetics of nerve growth factor (NGF) in mice. Methods: 12 5I NGF by chloramine T method by intravenous and intramuscular injection of two ways, the concentration of plasma NGF using isotope tracing combined with trichloroacetic acid (TCA) precipitation or SDS PAGE electrophoresis, the determination of plasma NGF concentration. Results: The half-life of t1 / 2 β was determined by electrophoresis and the acid-precipitation method was 2.26 h after the intravenous injection of 125I NGF 2 μg / kg. The half-life t1 / 2 β of the intramuscular injection of 125I NGF75, 25, 100 μg · kg-1 were respectively 2.14, 2.331 and 3.1 73 h by electrophoresis, and the elimination half-life t1 / 2 β were respectively 2.48, 2.55 2 and 2.62 42h, and the peak time tmax was 0.53 83h. The average plasma clearance (Cl) of 125I NGF was 0.321 and 0.322L · h-1 · kg-1 respectively by electrophoresis and acid sedimentation. The apparent volume of distribution (Vd) was 1.259 And 1.31 5L · kg-1, respectively. The mean in vivo MRTs were 3.592 and 3.539 hours, respectively. Conclusion: NGF has short elimination half-life in vivo. This study provides the necessary reference for future clinical application.