Smith R M, Spragg R G, Moser K M, Cochrane C G, McCarren J P
Department of Medicine, University of California at San Diego.
Am Rev Respir Dis. 1987 Dec;136(6):1391-6. doi: 10.1164/ajrccm/136.6.1391.
To study the penetration of alpha 1-proteinase inhibitor (A1Pl) into the lungs of healthy dogs, 83 mg/kg of active A1Pl was administered intravenously over 30 min followed by a bolus of 131I-A1Pl. Animals were lavaged 2 to 72 h after infusion, sequential gamma camera scans were acquired, and urine was analyzed for the excretion of desmosine. After a distribution phase, infused A1Pl left the bloodstream with a half-life of 103 +/- 24 h. Analysis of plasma antiprotease activity demonstrated preservation of function of the infused A1Pl. Lavage fluid A1Pl concentration and activity were significantly increased 24 h after infusion. Gamma camera scans demonstrated that lung, liver, and spleen acquired 131I-A1Pl similarly; radioactivities per gram of tissue of these organs were similar at autopsy. Excretion of desmosine did not decrease from a baseline of 157 +/- 59 nmol/24 h after A1Pl infusion, indicating no effect of A1Pl infusion on background elastolysis. These data suggest that intravenous administration of A1Pl can raise lung antiproteinase levels within 24 h despite the absence of preferential uptake by the lung of the infused protein.
为研究α1-蛋白酶抑制剂（A1Pl）在健康犬肺内的渗透情况，在30分钟内静脉注射83mg/kg活性A1Pl，随后推注131I-A1Pl。在输注后2至72小时对动物进行灌洗，进行连续γ相机扫描，并分析尿液中锁链素的排泄情况。在分布阶段后，输注的A1Pl以103±24小时的半衰期离开血液循环。血浆抗蛋白酶活性分析表明输注的A1Pl功能得以保留。输注后24小时灌洗液中A1Pl浓度和活性显著升高。γ相机扫描显示肺、肝和脾摄取131I-A1Pl的情况相似；这些器官每克组织的放射性在尸检时相似。A1Pl输注后锁链素的排泄量未从157±59nmol/24小时的基线水平下降，表明A1Pl输注对基础弹性蛋白溶解无影响。这些数据表明，尽管输注的蛋白质未被肺优先摄取，但静脉注射A1Pl仍可在24小时内提高肺抗蛋白酶水平。
