Decreased survival in vivo of diamide-incubated dog erythrocytes. A model of oxidant-induced hemolysis.
Decreased survival in vivo of diamide-incubated dog erythrocytes. A model of oxidant-induced hemolysis.
复制标题
二酰胺孵育的狗红细胞体内存活率降低。
DOI：
10.1172/jci109964
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发表时间：
1980
期刊：
影响因子：
--
通讯作者：
White,JG
中科院分区：
文献类型：
--
作者：
Johnson,GJ;Allen,DW;Flynn,TP;Finkel,B;White,JG
葡萄糖-6-磷酸脱氢酶（G-6-PD）缺乏的慢性溶血性变体患者的红细胞具有结构性膜蛋白异常，伴有细胞膜变形能力降低，我们假设这代表氧化剂诱导的膜损伤的后果。为了评价氧化剂引起的膜损伤的病理生理意义，我们研究了巯基氧化剂，联胺，对狗红细胞的体外和体内影响。犬红细胞与0.4 mM二酰胺在Tris缓冲盐水中于37 ℃下体外孵育90 min，导致GSH耗竭，形成膜多肽聚集体（440，000和> 50，000，000道尔顿），并降低细胞微管可变形性，这些异常与G-6-PD缺乏的慢性溶血性变体患者红细胞中观察到的异常相似。此外，二酰胺孵育的细胞具有增加的粘度和增加的膜比重，但ATP没有变化。再注射51铬标记，二酰胺孵育的细胞，随后显着缩短在体内的生存和脾隔离。在4 mM二硫苏糖醇中进一步孵育二酰胺孵育的细胞逆转了膜多肽聚集体，使微量移液管变形性正常化，降低了细胞粘度，延长了体内存活时间，并降低了脾隔离。这些研究表明，联胺诱导部分可逆的红细胞损伤，这是一个有用的模型氧化剂诱导的膜损伤。他们认为氧化剂诱导的红细胞膜损伤在慢性溶血的病理生理学中起着重要作用，伴随着一些G-6-PD变体。图片
Erythrocytes from patients with chronic hemolytic variants of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency have structural membrane protein abnormalities accompanied by decreased cell membrane deformability which we postulate represent the consequences of oxidant-induced membrane injury. To evaluate the pathophysiologic significance of oxidant-induced membrane injury, we studied the in vitro and in vivo effects of the thiol-oxidizing agent, diamide, on dog erythrocytes. In vitro incubation of dog erythrocytes with 0.4 mM diamide in Tris-buffered saline for 90 min at 37 degrees C resulted in depletion of GSH, formation of membrane polypeptide aggregates (440,000 and > 50,000,000 daltons) and decreased cell micropipette deformability, abnormalities similar to those observed in the erythrocytes of patients with chronic hemolytic variants of G-6-PD deficiency. In addition, diamide-incubated cells had increased viscosity and increased membrane specific gravity, but no change in ATP. Reinjection of 51Cr-labeled, diamide-incubated cells was followed by markedly shortened in vivo survival and splenic sequestration. Further incubation of diamide-incubated cells in 4 mM dithiothreitol reversed the membrane polypeptide aggregates, normalized micropipette deformability, decreased cell viscosity, prolonged in vivi survival, and decreased splenic sequestration. These studied demonstrate that diamide induces a partially reversible erythrocyte lesion which is a useful model of oxidant-induced membrane injury. They suggest that oxidant-induced erythrocyte membrane injury plays an important role in the pathophysiology of chronic hemolysis which accompanies some G-6-PD variants.Images