PLASMA-CLEARANCE, TISSUE DISTRIBUTION AND METABOLISM OF HYALURONIC-ACID INJECTED INTRAVENOUSLY IN THE RABBIT
PLASMA-CLEARANCE, TISSUE DISTRIBUTION AND METABOLISM OF HYALURONIC-ACID INJECTED INTRAVENOUSLY IN THE RABBIT
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DOI：
10.1042/bj2000415
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发表时间：
1981-01-01
影响因子：
4.1
通讯作者：
BAXTER, E
中科院分区：
文献类型：
--
作者：
FRASER, JRE;LAURENT, TC;BAXTER, E
研究了高平均分子量透明质酸的血浆清除率、组织分布和代谢。[3 H]乙酰标记的透明质酸在滑膜细胞培养物中合成。在兔中静脉内注射后，标记物从血浆中消失，半衰期为2.5-4.5分钟，这对应于正常的透明质酸清除率约为10 mg/天/kg体重注射未标记的透明质酸15分钟后，示踪剂未能扭转其吸收。标记的聚合物的清除通过预先注射过量的未标记的透明质酸而延迟。在这种情况下，最大清除能力估计为. apprx。30 mg/天/kg体重注射的材料集中在肝脏和脾脏中。多达88%的标记物被肝脏吸收，几乎完全在非实质细胞中发现。降解是快速和完整的，因为挥发性物质，大概是3 H2O，出现在血浆中20分钟内。未降解的[3 H]透明质酸，小标记残留物和3 H2O中检测到肝脏，但几乎没有证据表明中间寡糖。在血浆或尿液中未识别出除3 H2O外的代谢产物。24小时后，三分之二的放射性保留在体液中，在肝脏脂质中发现少量放射性。脾脏中的放射性下降速度不及肝脏。肾脏排泄的MW上限为约25,000.肾脏排泄在清除中的作用可以忽略不计。透明质酸从血浆中去除，并通过主要位于肝脏中的具有高储备能力的有效肾外系统快速降解。
The plasma clearance, tissue distribution and metabolism of hyaluronic acid were studied with a high average MW. [3H]acetyl-labeled hyaluronic acid synthesized in synovial cell cultures. After i.v. injection in the rabbit, the label disappeared from the plasma with a half-life of 2.5-4.5 min, which corresponds to a normal hyaluronic acid clearance of .apprx. 10 mg/day per kg body wt. Injection of unlabeled hyaluronic acid 15 min after the tracer failed to reverse its absorption. Clearance of labeled polymer was retarded by prior injection of excess unlabeled hylauronic acid. The maximum clearance capacity was estimated in these circumstances to be .apprx. 30 mg/day per kg body wt. The injected material was concentrated in the liver and spleen. As much as 88% of the label was absorbed by the liver, where it was found almost entirely in nonparenchymal cells. Degradation was rapid and complete, since volatile material, presumably 3H2O, appeared in the plasma within 20 min. Undegraded [3H]hyaluronic acid, small labeled residues and 3H2O were detected in the liver, but there was little evidence of intermediate oligosaccharides. No metabolite except 3H2O was recognized in plasma or urine. Two-thirds of the radioactivity was retained in the body water 24 h later and small amounts were found in liver lipids. Radioactivity did not decline in the spleen as rapidly as in the liver. The upper MW limit for renal excretion was .apprx. 25,000. Renal excretion played a negligible part in clearance. Hyaluronic acid is removed from the plasma and degraded quickly by an efficient extrarenal system with a high reserve capacity, sited mainly in the liver.