Hsu Mei-Hsin, Chen Yu-Chieh, Sheen Jiunn-Ming, Li Shih-Wen, Huang Li-Tung
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung.
Department of Traditional Medicine, Chang Gung University, Linkow, Taiwan.
Neuroreport. 2018 May 2;29(7):541-546. doi: 10.1097/WNR.0000000000000972.
Bile duct ligation (BDL) in young rats can cause impaired liver function and cognition deficits. Nitric oxide is implicated in hepatic encephalopathy and is also involved in cognition. In this study, we examined the role of brain asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, in young BDL rats with spatial deficits. Young male Sprague-Dawley rats aged 17 days were assigned to four groups: laparotomy (SHAM), laparotomy plus 5 mg melatonin delivered through a pellet (SHAMM) for 4 weeks, BDL for 4 weeks, and BDL plus 5 mg melatonin delivered through a pellet (BDLM) for 4 weeks. Their spatial memory was assessed using a Morris water-maze task. Plasma and brains were collected for biochemical and ADMA analyses. We found that the BDL group had significantly elevated levels of ADMA in the plasma, the prefrontal cortex, and the dorsal hippocampus, and worse spatial performance than that of the control groups. Melatonin administration prevented an increase in the ADMA levels in the plasma, prefrontal cortex, and dorsal hippocampus, and prevented spatial deficits in BDL rats. In addition, melatonin maintained brain-derived neurotrophic factor in the dorsal hippocampus at a level comparable with controls. We concluded that melatonin is effective in preventing spatial deficits and decreasing ADMA levels in the plasma, prefrontal cortex, and dorsal hippocampus in young BDL rats. Brain ADMA levels might play a role in BDL-induced spatial deficits.
幼鼠胆管结扎（BDL）可导致肝功能受损和认知缺陷。一氧化氮与肝性脑病有关，也参与认知过程。在本研究中，我们研究了内源性一氧化氮合酶抑制剂——脑不对称二甲基精氨酸（ADMA）在患有空间缺陷的幼龄BDL大鼠中的作用。将17日龄的雄性幼龄Sprague-Dawley大鼠分为四组：假手术组（SHAM）、假手术加通过植入物给予5mg褪黑素组（SHAMM），持续4周；BDL组，持续4周；BDL加通过植入物给予5mg褪黑素组（BDLM），持续4周。使用Morris水迷宫任务评估它们的空间记忆。收集血浆和大脑进行生化和ADMA分析。我们发现，BDL组血浆、前额叶皮质和背侧海马中的ADMA水平显著升高，且空间表现比对照组差。给予褪黑素可防止血浆、前额叶皮质和背侧海马中ADMA水平升高，并防止BDL大鼠出现空间缺陷。此外，褪黑素使背侧海马中的脑源性神经营养因子维持在与对照组相当的水平。我们得出结论，褪黑素可有效预防幼龄BDL大鼠的空间缺陷，并降低血浆、前额叶皮质和背侧海马中的ADMA水平。脑ADMA水平可能在BDL诱导的空间缺陷中起作用。
