摘要
用12 5I 标记单链尿激酶型纤溶酶原激活剂 ( 12 5I labelledsingle chainhumanrecombi nanturokinase typeplasminogenactivator ,( 12 5I rh sc uPA)研究单次静脉推注后三氯醋酸 (TCA)可沉淀放射性在兔体内各组织分布的时间过程。方法 :Iodogen法制备12 5I rh sc uPA ,SephacrylS 2 0 0HR分离纯化 ,反相高效液相鉴定放射化学纯度 ,纤维蛋白平板法测定标记物的生物活性。结果 :制备了符合药代动力学研究要求、有体外溶纤维蛋白活性的12 5I rh sc uPA ,放射化学纯度为94 .4 %。检测灵敏度为 5Bq/g新鲜组织 ,各组织标准曲线的相关系数r >0 .999,回收率 >80 %。分布实验表明 ,酸可沉淀放射性按高到低排列依次为肾 >尿 >血清 >肝 >脾 >肾上腺 >骨髓 >心脏 >膀胱 >肺 >生殖腺 >小肠壁 >脂肪 >淋巴结 >胆囊 >胸腺 >肠内容 >肌肉 >肠内粪 >脑。结论 :静脉推注 12 5 I rh sc uPA后溶栓靶器官血液中的酸可沉淀放射性浓度较高 ,药物主要通过泌尿系统排泄。
Objective: To study tissue distribution profiles of trichloroacetic acid (TCA) precipitated radioactivity in rabbits following intravenous injection of 125 I labeled single chain human recombinant urokinase type plasminogen activator ( 125 I rh sc uPA). Methods: 125 I rh su uPA was prepared by Iodogen method and was purified by Saphacryl HR S 200. The radio chemical purity was measured by reverse phase high performance liquid chromatography (RP HPLC). Biological activity of labeled protein was measured by thrombolytic activity on fibrin plate. Results: The identification of 125 I rh sc uPA revealed that it was a 94.4 % radio chemically purified thrombolytic active protein. The AUC of radioactivity gradients in tissues and other specimens were as follows: kidney>urine>plasma>liver>spleen>adrenal gland>bone marrow>heart>urinary bladder>lungs>gonad>small intestinal wall>fat>lymph node>gall bladder>thymus gland>intestinal content>muscle>brain>feces in colon. Conclusion: The highest TCA precipitated radioactivity was found in plasma following iv of 125 I rh u PA, which might be favorable for the drug action. The main excretion route was urinary system. [
出处
《军事医学科学院院刊》
CSCD
北大核心
2000年第2期102-104,152,共4页
Bulletin of the Academy of Military Medical Sciences
