Alterations in NADPH oxidase expression and blood-brain barrier in bile duct ligation-treated young rats: Effects of melatonin

被引:17
作者
Chen, Yu-Chieh [1 ]
Sheen, Jiunn-Ming [1 ,2 ]
Tain, You-Lin [1 ]
Chen, Chih-Cheng [1 ]
Tiao, Miao-Meng [1 ]
Huang, Ying-Hsien [1 ]
Hsieh, Chih-Sung [3 ,4 ]
Huang, Li-Tung [1 ,5 ]
机构
[1] Kaohsiung Chang Gung Mem Hosp, Dept Pediat, Kaohsiung, Taiwan
[2] Chang Gang Univ Coll Med, Grad Inst Clin Med Sci, Kaohsiung, Taiwan
[3] Pingtung Christian Hosp, Dept Pediat Surg, Pingtung, Taiwan
[4] MeiHo Univ, Pingtung, Taiwan
[5] Chang Gang Univ, Dept Tradit Chinese Med, Linkow, Taiwan
关键词
Bile duct ligation; Cholestasis; Superoxide; Blood-brain barrier; Melatonin; INDUCED OBSTRUCTIVE-JAUNDICE; SOLUBLE GUANYLATE-CYCLASE; OXIDATIVE STRESS; HEPATIC-ENCEPHALOPATHY; CIRRHOTIC-PATIENTS; ENDOTHELIAL-CELLS; LIVER-DISEASE; AMMONIA; HYPERAMMONEMIA; PERMEABILITY;
D O I
10.1016/j.neuint.2012.03.021
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Bile duct ligation (BDL)-treated rats exhibit cholestasis and increased systemic and brain oxidative stress. Activation of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase and disruption of the blood-brain barrier (BBB) are implicated as the pathogenetic mechanisms of brain dysfunction in BDL-treated adult rats. Young rats underwent sham ligation or BDL at day 17 for 2 or 4 weeks. Treatment group rats were administered melatonin between day 17 and 45. We found a progressive increase in prefrontal cortex NADPH-dependent superoxide anion (O-2(-)) production and increased expression of NADPH oxidase subunits in either the prefrontal cortex or the hippocampus in BDL-treated young rats. In addition, expression of intercellular adhesion molecule-1 (ICAM) and tissue plasminogen activator (t-PA) genes were increased in either the prefrontal cortex or the hippocampus. Prefrontal cortex capillary junctional complex proteins expressions including occludin, claudin-5, platelet endothelial cell adhesion molecule-1 and vascular endothelial cadherin were not altered. Melatonin lowered the prefrontal cortex NADPH-dependent O-2(-) production and t-PA gene expression. We conclude that alterations in NADPH oxidase expression and BBB are involved in brain dysfunction in BDL-treated young rats. In addition, melatonin regulates NADPH oxidase activity and t-PA gene expression. (C) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码:751 / 758
页数:8
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