Lim Y K, Jenner A, Ali A B, Wang Y, Hsu S I, Chong S M, Baumman H, Halliwell B, Lim S K
National University Medical Institutes, The National University of Singapore.
Kidney Int. 2000 Sep;58(3):1033-44. doi: 10.1046/j.1523-1755.2000.00261.x.
Haptoglobin knockout (Hp-/-) mice are more sensitive to phenylhydrazine-induced hemolysis than Hp+/+ mice.
Hemolysis was induced in Hp-/- and Hp+/+ mice using phenylhydrazine. Relative renal tissue damage and function were then assessed.
Hp-/- mice had higher basal levels of renal lipid peroxidation, as evidenced by levels of malonaldehyde and 4-hydroxy-2(E)-nonenal (MDA/HNE). After the administration of phenylhydrazine, levels of 8-hydroxyguanine (but not other products of oxidative DNA damage) were significantly elevated in the renal DNA. There was also increased induction of heme oxygenase-1. The more severe renal damage in Hp-/- mice was also evident in the delayed erythropoietin gene expression and poorer renal clearance of 3H-inulin. This reduction in glomerular filtration function in Hp+/+ and Hp-/- mice could be restored to baseline by vasodilators (prazosin or diazoxide), implicating renal vasoconstriction as a major mechanism of acute renal failure during induced hemolysis. Precipitation of hemoglobin in the kidney was not increased in Hp-/- mice.
Haptoglobin appears to play an important physiological role as an antioxidant, particularly during hemolysis.
与 Hp+/+ 小鼠相比，触珠蛋白基因敲除（Hp-/-）小鼠对苯肼诱导的溶血更敏感。
使用苯肼在 Hp-/- 和 Hp+/+ 小鼠中诱导溶血。然后评估相对肾组织损伤和功能。
Hp-/- 小鼠的肾脂质过氧化基础水平较高，丙二醛和 4-羟基-2（E）-壬烯醛（MDA/HNE）水平证明了这一点。给予苯肼后，肾 DNA 中 8-羟基鸟嘌呤（但不是氧化 DNA 损伤的其他产物）水平显著升高。血红素加氧酶-1 的诱导也增加。Hp-/- 小鼠更严重的肾损伤在促红细胞生成素基因表达延迟和 3H-菊粉的肾清除率较差方面也很明显。Hp+/+ 和 Hp-/- 小鼠肾小球滤过功能的这种降低可以通过血管扩张剂（哌唑嗪或二氮嗪）恢复到基线，这表明肾血管收缩是诱导溶血期间急性肾衰竭的主要机制。Hp-/- 小鼠肾脏中血红蛋白的沉淀没有增加。
触珠蛋白似乎作为一种抗氧化剂发挥重要的生理作用，特别是在溶血期间。
