大鼠脑线粒体膜氧化胆红素的遗传变异

Thor Willy Ruud Hansen , Steve Tommarello, Jeffrey W. Allen
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引用次数: 15

摘要

胆红素被脑线粒体膜氧化,其氧化速率可能对脑内胆红素的清除有重要作用。不同品系的先天性黄疸大鼠(Gunn大鼠)在纯合子(黄疸)幼鼠的死亡率方面差异很大。由于脑内氧化胆红素的能力可以防止毒性,我们假设氧化胆红素的能力在Gunn大鼠品系(ACI/N-j)中较低,在纯合子幼崽中死亡率较高。用蔗糖梯度差离心法从幼鼠脑中获得线粒体。超声使线粒体破裂。在加入膜悬浮液后,测量了胆红素溶液在440 nm处的光密度随时间的变化。与ACI/N-j和Sprague-Dawley菌株相比,RHA/N-j菌株7-8日龄大鼠和成年大鼠胆红素氧化率均显著降低。Gunn大鼠RHA/N-j和ACI/N-j菌株之间的死亡率差异不能用脑线粒体膜氧化胆红素能力的差异来解释,因为RHA/N-j大鼠的胆红素活性较低,死亡率也较低,而ACI/N-j大鼠的胆红素活性较高,死亡率非常高。这项研究也证实了先前的研究结果与年龄成熟的酶活性有关。
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Oxidation of Bilirubin by Rat Brain Mitochondrial Membranes—Genetic Variability

Bilirubin is oxidized by brain mitochondrial membranes at a rate which may contribute significantly to clearance of bilirubin from brain. Different strains of congenitally jaundiced rats (Gunn rats) vary widely as far as the mortality rate of the homozygous (jaundiced) pups. Because the ability to oxidize bilirubin in brain may protect against toxicity, we hypothesized that the ability to oxidize bilirubin would be lower in Gunn rat strains (ACI/N-j) with a high mortality rate in the homozygous pups. Mitochondria were obtained from young rat brains by differential centrifugation in sucrose gradients. The mitochondria were ruptured by sonication. The change in optical density of a bilirubin solution at 440 nm was measured over time following addition of the membrane suspension. The rate of bilirubin oxidation was significantly lower in rats of the RHA/N-j strain both at 7–8 days of age and in adults, compared to rats of the ACI/N-j and the Sprague-Dawley strains at the same age points. Differences in mortality rates between the RHA/N-j and the ACI/N-j strains of Gunn rats could not be explained on the basis of differences in the ability of brain mitochondrial membranes to oxidize bilirubin, as these activities were lower in the RHA/N-j rats, which also have lower mortality rates, but higher in the ACI/N-j rats, which have remarkably high mortality rates. This study also confirmed previous findings relative to age maturation of the enzyme activity.

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