卟啉症的酶替代疗法——V。用载酶红细胞鬼影在体内纠正铅中毒动物红细胞中氨酰戊酸脱水酶缺陷。

Drug design and delivery Pub Date : 1989-12-01
N L Bustos, A M Batlle
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引用次数: 0

摘要

再密封红细胞鬼是外源性治疗酶的潜在体内载体。本研究研究了经自体红细胞鬼(RBCg)包封的δ -氨基乙酰戊酸脱水酶(ALA-D)对铅中毒小鼠和正常小鼠的影响。给中毒小鼠注入含有ALA-D的RBCg后,红细胞ALA-D活性立即和永久恢复;这种作用在肝脏和脾脏中也很明显,而在肾脏中则不存在,这表明被包裹的酶被显著稳定,从而使循环细胞和被吞噬细胞的活性得以保留。给正常小鼠注入ALA-D后,血液、肝脏、脾脏和肾脏中ALA-D活性均未发生显著变化。在铅中毒期间给予游离外源性酶或输血也是无效的;中毒动物的自然恢复非常缓慢。我们表明,循环和吞噬的ALA-D包裹在自体红细胞鬼可以安全有益的治疗铅中毒。建议对患者进行临床试验。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Enzyme replacement therapy in porphyrias--V. In vivo correction of delta-aminolaevulinate dehydratase defective in erythrocytes in lead intoxicated animals by enzyme-loaded red blood cell ghosts.

Resealed erythrocyte ghosts are potential in vivo carriers of exogenous therapeutic enzymes. In the present work, the effect of administering delta-aminolaevulinate dehydratase (ALA-D) encapsulated in autologous red blood cell ghosts (RBCg) to lead intoxicated and normal mice was investigated. Administration of ALA-D loaded RBCg to intoxicated mice produced an immediate and permanent recovery in erythrocytic ALA-D activity; the effect was also noticeable in liver and spleen and absent in kidney, indicating that the entrapped enzyme was significantly stabilized to allow retention of activity in both circulating and phagocytized cells. Administration of ALA-D loaded ghosts to normal mice did not produce significant changes in ALA-D activity in blood, liver, spleen or kidney. Administration of free exogenous enzyme or blood transfusion during lead intoxication was also ineffective; spontaneous recovery of the poisoned animals was very slow. We show that circulating as well as phagocytized ALA-D entrapped in autologous erythrocyte ghosts can be safe and beneficial in the treatment of lead poisoning. Clinical trial in patients is recommended.

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