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

作者：Chen Yu Chieh; Sheen Jiunn Ming; Tain You Lin; Chen Chih Cheng; Tiao Miao Meng; Huang Ying Hsien; Hsieh Chih Sung; Huang Li Tung^*

来源：Neurochemistry International, 2012, 60(8): 751-758.

DOI：10.1016/j.neuint.2012.03.021

• Bile duct ligation
• Cholestasis
• Superoxide
• Blood-brain barrier
• Melatonin

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.

• 出版日期2012-6