Jamal Mostofa, Ameno Kiyoshi, Ikuo Uekita, Kumihashi Mitsuru, Wang Weihuan, Ijiri Iwao
Department of Forensic Medicine, Faculty of Medicine, Kagawa Universiy, Ikenobe, Miki, Kita, Kagawa 761-0793, Japan.
Novartis Found Symp. 2007;285:137-41; discussion 141-4, 198-9. doi: 10.1002/9780470511848.ch10.
First, ethanol (EtOH) and acetaldehyde levels were determined simultaneously in the striatum of free-moving rats after administration of their major oxidative enzyme inhibitors followed by EtOH. The results showed that acetaldehyde was present in the cyanamide (CY) + EtOH, CY + 4-methylpyrazole (4-MP) + EtOH and CY + sodium azide + EtOH groups. The CY + EtOH-induced peak acetaldehyde level was 195.2 +/- 19.4 microM, and this value was significantly higher than those in the other groups. The peak EtOH level was 25.9 +/- 2.3mM in the CY + 4-MP + EtOH group, and this level was considerably higher than the value in EtOH. No significant difference in brain EtOH levels was found in any of the other groups studied. Second, the effects of EtOH and acetaldehyde on choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were investigated in the frontal cortex and hippocampus of high acetaldehyde-producing rats using RT-PCR and Western blot. The results showed that EtOH and acetaldehyde decreased ChAT expression at 40 and 240 min after EtOH dosing in the brain. The acetaldehyde-induced reduction in ChAT expression was significantly higher than that induced by EtOH. No remarkable alteration of AChE expression was observed. The study suggested that catalase made a significant contribution to acetaldehyde formation in the rat brain, and that EtOH and acetaldehyde decreased ChAT expression at 40 and 240 min after EtOH dosing.
首先,在自由活动的大鼠给予主要氧化酶抑制剂后再给予乙醇(EtOH),同时测定纹状体中的乙醇和乙醛水平。结果显示,在氨基氰(CY)+乙醇、CY + 4 - 甲基吡唑(4 - MP)+乙醇以及CY +叠氮化钠+乙醇组中存在乙醛。CY +乙醇诱导的乙醛峰值水平为195.2±19.4微摩尔,该值显著高于其他组。CY + 4 - MP +乙醇组中的乙醇峰值水平为25.9±2.3毫摩尔,此水平明显高于乙醇组的值。在所研究的其他任何组中,脑乙醇水平均未发现显著差异。其次,使用逆转录聚合酶链反应(RT - PCR)和蛋白质免疫印迹法(Western blot),在高乙醛生成大鼠的额叶皮质和海马体中研究了乙醇和乙醛对胆碱乙酰转移酶(ChAT)和乙酰胆碱酯酶(AChE)的影响。结果显示,乙醇给药后40分钟和240分钟时,乙醇和乙醛降低了脑中ChAT的表达。乙醛诱导的ChAT表达降低显著高于乙醇诱导的降低。未观察到AChE表达有明显改变。该研究表明,过氧化氢酶对大鼠脑中乙醛的形成有显著贡献,并且乙醇给药后40分钟和240分钟时,乙醇和乙醛降低了ChAT的表达。