Intravascular recovery of VWF and FVIII following intraperitoneal injection and differences from intravenous and subcutaneous injection in mice.
Intravascular recovery of VWF and FVIII following intraperitoneal injection and differences from intravenous and subcutaneous injection in mice.
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DOI：
10.1111/j.1365-2516.2011.02735.x
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发表时间：
2012-07
期刊：
影响因子：
--
通讯作者：
Montgomery RR
中科院分区：
文献类型：
--
作者：
Shi Q;Kuether EL;Schroeder JA;Fahs SA;Montgomery RR
人体静脉输注研究表明，与其他凝血蛋白相比，VWF和FVIII均保留在血管内。我们探讨了通过腹膜内（IP）或皮下（SC）注射输注VWF和FVIII是否会导致这些大蛋白质有效吸收到血管循环中。通过IP、SC或静脉内（IV）注射向FVIIInull或VWF null小鼠输注血浆来源的或重组VWF和/或FVIII。IP注射后，VWF和FVIII均被吸收到血液循环中，在2至4小时之间达到峰值，水平与静脉输注小鼠中观察到的水平相似。相比之下，SC注射后血浆中未检测到VWF和FVIII。尽管IV注射快速达到血浆峰值水平，但在IV注射后的前2小时内，人VWF和FVIII均迅速下降。IV和IP输注VWF后，循环VWF的多聚体结构与输注液中观察到的相似。这些结果表明，IP注射后，VWF和FVIII均可有效吸收至血液循环中，但SC注射后不能，表明IP给药可能是VWF或FVIII输注的替代途径。
Intravenous infusion studies in humans suggest that both VWF and FVIII remain intravascular in contrast to other coagulation proteins. We explored whether infusion of VWF and FVIII by either intraperitoneal (IP) or subcutaneous (SC) injection would result in efficient absorption of these large proteins into the vascular circulation. FVIIInull or VWFnull mice were infused with plasma-derived or recombinant VWF and/or FVIII by IP, SC, or intravenous (IV) injection. Both VWF and FVIII were absorbed into the blood circulation after IP injection with a peak between 2 to 4 hours at levels similar to those observed in mice infused intravenously. In contrast, neither VWF nor FVIII was detected in the plasma following SC injection. Although IV injection achieved peak plasma levels quickly, both human VWF and FVIII rapidly decreased during the first 2 hours following IV injection. Following both IV and IP infusion of VWF, the multimeric structure of circulating VWF was similar to that observed in the infusate. These results demonstrate that both VWF and FVIII can be efficiently absorbed into the blood circulation following IP but not SC injection, indicating that IP administration could be an alternative route for VWF or FVIII infusion.
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