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目的研究人工合成胸腺素α1(synthetic thymosin alpha 1,sTα1)在小鼠和大鼠体内静脉注射的分布和排泄特点。方法用竞争ELISA法测定sTα1在小鼠体内静脉注射后不同时间点组织中的药物浓度和不同时间段内尿液药物累计量;同法检测sTα1在大鼠体内静脉注射后不同时间段内胆汁药物累计量。结果分布特点:小鼠sTα1静脉注射后15 min时胸腺中药物分布最高,浓度为(1 533.4±712.4)ng/g,肝、脾、胸腺次之,在脑中含量较低;静脉注射后30 min时胸腺组织中药物分布依然最高,浓度为(25 583.4±6 244.7)ng/g,脾、肾、肝中次之。sTα1静脉注射后1 h时肾脏中药物分布最高,浓度为(6 164.1±4 821.8)ng/g,胸腺浓度为(5 665.8±3 881.9)ng/g。静脉注射后2 h时肾脏分布最高,浓度为(1 408.0±1 252.7)ng/g,而胸腺中浓度仅为(306.4±268.6)ng/g,其他组织中有少量分布,脑组织中的药物浓度接近血浆药物浓度,说明sTα1可通过血脑屏障。排泄特点:小鼠静脉注射sTα1 1 mg/kg后,12 h尿累计排泄量为给药量的26.35%,大鼠静脉注射0.5 mg/kg sTα1后,胆汁中未见有药物排出。结论小鼠静脉注射sTα1后可以浓集于免疫器官胸腺和脾脏内,且可进入血脑屏障,以原型经肾排泄为主要排泄途径。
Objective To study the distribution and excretion of synthetic thymosin alpha 1 (sTα1) in mice and rats by intravenous injection. Methods The competitive ELISA method was used to determine the concentration of sTα1 in different time points after instillation of sTα1 in mice. The same method was used to detect the accumulation of sTα1 in different time periods after bortezomib Cumulative amount. RESULTS: The distribution of thymus was the highest in the thymus at 15 min after intravenous injection of sTα1, with the concentration of (1 533.4 ± 712.4) ng / g, followed by the liver, spleen and thymus, and lower in the brain. min, the drug distribution in thymus tissue was still the highest (25 583.4 ± 6 244.7) ng / g, followed by spleen, kidney and liver. At 1 h after intravenous injection of sTα1, the distribution of the drug in kidney was the highest (6 164.1 ± 4821.8 ng / g) and the thymus (5 665.8 ± 3 881.9) ng / g. At 2 h after intravenous injection, the kidney distribution was the highest (1 408.0 ± 1 252.7) ng / g, while that in the thymus was only (306.4 ± 268.6) ng / g. There was a small amount of distribution in other tissues. Concentration close to the plasma drug concentration, indicating that sTα1 can cross the blood-brain barrier. Excretion characteristics: mice intravenous injection of sTα1 1 mg / kg, 12 h urine cumulative dose of 26.35% of the dose, intravenous injection of 0.5 mg / kg sTα1 rats, bile no drug discharge. Conclusion Intravenous injection of sTα1 in mice can be concentrated in the thymus and spleen of immune organs, and can enter the blood-brain barrier. The prototype is excreted by the kidneys as the main excretion pathway.