Increased susceptibility in Hp knockout mice during acute hemolysis
Increased susceptibility in Hp knockout mice during acute hemolysis
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DOI：
10.1182/blood.v92.6.1870.418k38_1870_1877
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发表时间：
1998-09-15
期刊：
影响因子：
20.3
通讯作者：
Baumman, H
中科院分区：
文献类型：
--
作者：
Lim, SK;Kim, HK;Baumman, H
结合珠蛋白是一种保守的血浆糖蛋白，与游离血浆血红蛋白形成非常稳定的可溶性复合物。结合珠蛋白与血红蛋白的结合被认为在血红蛋白从血浆中的快速肝脏清除和抑制血红蛋白的肾小球过滤中是重要的。为了评价这些功能，建立了结合珠蛋白敲除（-/-）小鼠。这些小鼠是可行的，但有一个小的，显着降低出生后的生存能力。与普遍的看法相反，缺乏触珠蛋白并不损害-/-小鼠中游离血浆血红蛋白的清除。苯肼诱导的严重溶血导致-/-和+/+小鼠肾小管细胞中广泛的血红蛋白沉淀，55%的-/-小鼠和18%的+/+小鼠死亡。一般而言，苯肼处理的-/-小鼠遭受更大的组织损伤，如诱导肝脏急性期反应导致血浆α 1-酸性糖蛋白（AGP）水平升高所证明的。在存活的-/-和+/+小鼠中，-/-小鼠倾向于遭受更大的氧化损伤，并且不能修复或再生受损的肾组织，如分别由其较高的血浆丙二醛（MDA）和4-羟基-2（E）-壬烯醛（HNE）水平和较低的肾脏有丝分裂指数所指示的。这项研究表明，血红蛋白-触珠蛋白复合物形成的生理学重要作用是血红蛋白驱动的脂质过氧化作用的组织损伤的改善。(C)1998年，美国血液学会。
Haptoglobin, a conserved plasma glycoprotein, forms very stable soluble complexes with free plasma hemoglobin. Hemoglobin binding by haptoglobin is thought to be important in the rapid hepatic clearance of hemoglobin from the plasma and in the inhibition of glomerular filtration of hemoglobin. To evaluate these functions, Haptoglobin knockout (-/-) mice were created. These mice were viable but had a small, significant reduction in postnatal viability. Contrary to popular belief, the lack of haptoglobin did not impair clearance of free plasma hemoglobin in -/- mice. Induction of severe hemolysis by phenylhydrazine caused extensive hemoglobin precipitation in the renal tubular cells of both -/- and +/+ mice, with death occurring in 55% of -/- mice and in 18% of +/+ mice. In general, phenylhydrazine-treated -/- mice suffered greater tissue damage, as evidenced by the induction of hepatic acute phase response resulting in increased plasma alpha 1-acid glycoprotein (AGP) levels. Among -/- and +/+ mice that survived, -/- mice tend to suffer greater oxidative damage and failed to repair or regenerate damaged renal tissues, as indicated by their higher plasma malonaldehyde (MDA) and 4-hydroxy-2(E)-nonenal (HNE) levels and lower mitotic indices in their kidneys, respectively. This study Suggested that a physiologically important role;of hemoglobin-haptoglobin complex formation is the amelioration of tissue damages by hemoglobin-driven lipid peroxidation. (C) 1998 by The American Society of Hematology.