碘标记示踪沉淀法研究神经生长因子的药代动力学

Pharmacokinetics of Nerve Growth Factor by Iodolabelled Tracing Method

12 5 I-神经生长因子 (nerve growth factor,NGF)用氯胺 T法制备 ,采用同位素示踪结合三氯醋酸(TCA )沉淀法 ,测定小鼠血浆 NGF的浓度 ,并研究其在体内的分布与排泄。结果表明 ,静注 1 2 5 I- NGF,小鼠体内代谢符合二房室分布模型 ;肌注 1 2 5 I- NGF,小鼠体内代谢符合一房室分布模型。静注 1 2 5 I- NGF2 5 μg.kg- 1 ,测得消除半衰期 (t1 / 2 β)为 4.431h。肌注 1 2 5 I- N GF 75、2 5、10、3.3μg.kg- 1 ,测得消除半衰期 (t1 / 2 β)分别为 2 .135、2 .70 3、3.12 7、4.2 12 h,平均达峰时间 (tmax)为 0 .5 83h。测得 1 2 5 I- N GF平均血浆清除率 (CL)为 0 .2 77L.h- 1 .kg- 1 ,表观分布容积 (Vd)为 1.0 39L.kg- 1 ,体内平均滞留时间 (MRT)为 3.2 38h。1 2 5 I- NGF在组织器官内的分布速率以颈上神经节分布最快 ,大脑、小脑、脊髓分布极低。1 2 5 I- NGF主要经尿液和粪便排泄 ,注射后 72 h内 ,小鼠粪尿中放射性总排泄量为 80 .36 % ,其中尿排泄量占 73.87%

To study the pharmacokinetics of nerve growth factor (NGF) in mice, 125 I NGF was prepared by Chloroamine T method,and measured by trichloroacetic acid (TCA) precipitation method after iv and im 125 I NGF. The results showed that concentration time curves after iv 125 I NGF were fitted to a 2 compartment model and those after im 125 I NGF were fitted to a 1 compartment model. After iv 125 I NGF 25 μg·kg -1 , the elimination half life time ( t 1/2 β) determined by TCA method was 4.431 h. After im 125 I NGF 75,25,10,3.3 μg·kg -1 ,the mean time to peak ( t max ) was 0.583 h, the t 1/2 β was 2.135,2.703,3.127 and 4.212 h, respectively. The mean plasma clearance (CL) measured by TCA method was 0.277 L·h -1 ·kg -1 , the appearance volume of distribution (Vd) was 1.039 L·kg -1 and the mean residence time (MRT) was 3.238 h. After iv 125 I NGF, the highest levels of tissues distribution were in superior cervical ganglia, while the levels in cerebrum, cerebellum and spinal cord were lower. About 80.36% of the injected dose was excreted in excrement and urine within the first 72 h, of which 73.87% was excreted in urine.