胆汁淤积性肝病中氧化应激的系统性现象证据。
Evidence of a systemic phenomenon for oxidative stress in cholestatic liver disease.
作者信息
Ljubuncic P, Tanne Z, Bomzon A
机构信息
Department of Pharmacology, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
出版信息
Gut. 2000 Nov;47(5):710-6. doi: 10.1136/gut.47.5.710.
BACKGROUND
There is considerable evidence indicating that the severity of hepatic damage in individuals with cholestatic liver disease is causally associated with the extent of intrahepatic oxidative stress. Increased levels or accelerated generation of reactive oxygen species and toxic degradative products of lipid peroxidation have been reported in the plasma of individuals with chronic liver disease and animal models of liver disease. Hence, by virtue of their increased presence in the circulation, it is not unreasonable to suppose that they may account for extrahepatic tissue damage in chronic liver disease.
MATERIALS AND METHODS
This hypothesis was tested by determining plasma levels of the ubiquitous antioxidant glutathione (GSH) and lipid peroxides (LP), together with assessment of the extent of lipid peroxidation in the kidney, brain, and heart, in 24 day chronically bile duct ligated (CBDL) rats. The extent of lipid peroxidation in tissues was based on measurement of conjugated dienes, lipid peroxides, and malondialdehyde (MDA) content. Data were compared with identical data collected from unoperated control, pair fed, 24 day bile duct manipulated (sham operated), and pair fed sham operated rats.
RESULTS
In CBDL rats, total and reduced plasma GSH levels were almost half those determined in all control rats. Plasma, kidney, and heart LP levels were significantly increased in CBDL rats compared with controls. MDA levels were significantly higher in the kidney, brain, and heart homogenates prepared from CBDL rats compared with MDA content measured in tissue homogenates prepared from the four groups of control rats.
CONCLUSIONS
Our data show that experimental cholestatic liver disease is associated with increased lipid peroxidation in the kidney, brain, and heart. Hence we have concluded that the oxidative stress in cholestatic liver disease is a systemic phenomenon probably encompassing all tissues and organs, even those separated by the blood-brain barrier.
背景
有大量证据表明，胆汁淤积性肝病患者肝损伤的严重程度与肝内氧化应激程度存在因果关系。据报道，慢性肝病患者血浆及肝病动物模型中活性氧水平升高或脂质过氧化毒性降解产物生成加速。因此，鉴于它们在循环中的含量增加，推测它们可能导致慢性肝病的肝外组织损伤并非不合理。
材料与方法
通过测定24日龄慢性胆管结扎（CBDL）大鼠血浆中普遍存在的抗氧化剂谷胱甘肽（GSH）和脂质过氧化物（LP）水平，并评估肾脏、大脑和心脏的脂质过氧化程度，对这一假设进行了验证。组织中的脂质过氧化程度基于共轭二烯、脂质过氧化物和丙二醛（MDA）含量的测定。将数据与从未手术对照、配对喂养、24日胆管手术操作（假手术）及配对喂养假手术大鼠收集的相同数据进行比较。
结果
在CBDL大鼠中，血浆总GSH水平和还原型GSH水平几乎是所有对照大鼠测定值的一半。与对照组相比，CBDL大鼠血浆、肾脏和心脏的LP水平显著升高。与四组对照大鼠组织匀浆中测得的MDA含量相比，CBDL大鼠肾脏、大脑和心脏匀浆中的MDA水平显著更高。
结论
我们的数据表明，实验性胆汁淤积性肝病与肾脏、大脑和心脏脂质过氧化增加有关。因此我们得出结论，胆汁淤积性肝病中的氧化应激是一种全身性现象，可能涵盖所有组织和器官，甚至包括那些被血脑屏障分隔的组织和器官。
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