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胆红素与脑毛细血管的相互作用及其毒性。

Interaction of bilirubin with brain capillaries and its toxicity.

作者信息

Katoh-Semba R, Kashiwamata S

出版信息

Biochim Biophys Acta. 1980 Oct 1;632(2):290-7. doi: 10.1016/0304-4165(80)90087-2.

DOI:10.1016/0304-4165(80)90087-2
PMID:7417528
Abstract

The interaction of bilirubin with isolated brain capillaries, and the effect of bilirubin on the uptake of 2-deoxyglucose by the capillaries were investigated with 1-month-old Sprague-Dawley rats. The binding of bilirubin to the brain capillaries was observed only at a molar ratio of bilirubin to bovine serum albumin higher than 1.0. An absorption spectrum with a microspectrophotometer of the bilirubin-capillary complex showed a broad absorption maximum from 425 to 440 nm with a shoulder near 490 nm, but no shoulder was observed in the case of the bilirubin emulsion. The bilirubin binding activity was dependent on pH and temperature of the medium, but was not affected by sulfhydryl blocking agents such as p-chloromercuribenzoate and N-ethylmaleimide. Bilirubin saturation kinetics gave an apparent Km for bilirubin of 61.7 microM. Release of bilirubin from the brain capillaries to the medium was observed at 37 degrees C but not at 4 degrees C. The uptake of 2-deoxyglucose by the isolated brain capillaries was inhibited by bilirubin in a noncompetitive manner, giving an apparent Ki for the pigment of 137 microM. These results suggest that bilirubin may be responsible for the decreased 2-deoxyglucose uptake in the brain capillaries by disturbing the membrane structure of the capillary endothelial cells.

摘要

利用1月龄的斯普拉格-道利大鼠,研究了胆红素与离体脑毛细血管的相互作用,以及胆红素对毛细血管摄取2-脱氧葡萄糖的影响。仅在胆红素与牛血清白蛋白的摩尔比高于1.0时,才观察到胆红素与脑毛细血管的结合。用显微分光光度计测定的胆红素-毛细血管复合物的吸收光谱显示,在425至440nm处有一个宽的吸收最大值,在490nm附近有一个肩峰,但在胆红素乳剂的情况下未观察到肩峰。胆红素结合活性取决于介质的pH值和温度,但不受对氯汞苯甲酸和N-乙基马来酰亚胺等巯基阻断剂的影响。胆红素饱和动力学得出胆红素的表观Km为61.7μM。在37℃时观察到胆红素从脑毛细血管释放到介质中,但在4℃时未观察到。胆红素以非竞争性方式抑制离体脑毛细血管对2-脱氧葡萄糖的摄取,该色素的表观Ki为137μM。这些结果表明,胆红素可能通过扰乱毛细血管内皮细胞的膜结构,导致脑毛细血管中2-脱氧葡萄糖摄取减少。

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Interaction of bilirubin with brain capillaries and its toxicity.胆红素与脑毛细血管的相互作用及其毒性。
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