Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Rd., Stanford, CA 94305, USA.
Alcohol Clin Exp Res. 2010 Nov;34(11):1858-70. doi: 10.1111/j.1530-0277.2010.01274.x.
In rodent and human studies, ethanol (EtOH) exposure is associated with elevated brain levels of the magnetic resonance spectroscopy (MRS) signal representing choline-containing compounds (Cho). One interpretation of elevated brain Cho is that it is a marker of neuroinflammation, and some evidence suggests that EtOH exposure promotes neuroinflammation. This study aimed to determine whether binge EtOH exposure (intragastric 3 g/kg 25% EtOH every 8 hours for 4 days) would induce the expression of certain cytokines in blood, liver, or brain, thereby supporting the neuroinflammation hypothesis of elevated Cho.
Ten of 18 wild-type male Wistar rats (~322 g at baseline) were exposed to EtOH and attained average blood alcohol levels of ~315 mg/dl across 4 days. Blood for cytokine immunoassays was collected at baseline, after 5 doses of EtOH (binge), and immediately preceding euthanasia either 4 or 24 hours after the last dose of EtOH. Blood was additionally assayed for the levels of thiamine and liver enzymes; liver histopathology was performed postmortem; and tissue from liver and 6 brain regions was assayed for the potential induction of 7 cytokines.
There were no group effects on the levels of thiamine or its phosphate derivatives, thiamine monophosphate or thiamine diphosphate. ANOVAs of liver enzyme levels indicated that only alkaline phosphatase (ALP) levels were higher in the EtOH group than in control group at binge; ALP elevations, however, are difficult to explain in the absence of changes in the levels of additional liver enzymes. Postmortem liver pathology provided evidence for minimal microvesicular lipidosis and portocentric fibrosis in the EtOH group. Group effects on the levels of the measured cytokines in the blood (TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-13, and GRO/CXCL1) were not significant. Similarly, postmortem evaluation of liver cytokines did not reveal group effects. Postmortem evaluation of the 7 cytokines in 6 brain regions (anterior cerebellar vermis, cingulate cortex, frontal cortex, hippocampus, hypothalamus, striatum) also failed to identify group effects.
A single 4-day bout of binge EtOH exposure alone was insufficient to induce the expression of 7 cytokines in blood, liver, or 6 brain regions of wild-type Wistar rats. Alternative interpretations for elevations in brain Cho in response to a 4-day binge EtOH treatment are therefore necessary and may include induction of cytokines not measured herein or other noninflammatory mechanisms.
在啮齿动物和人类研究中，乙醇（EtOH）暴露与磁共振光谱（MRS）信号中代表含胆碱化合物（Cho）的水平升高有关。Cho 水平升高的一种解释是它是神经炎症的标志物，一些证据表明 EtOH 暴露会促进神经炎症。本研究旨在确定 binge EtOH 暴露（每隔 8 小时胃内给予 3 g/kg 25% EtOH，共 4 天）是否会诱导血液、肝脏或大脑中某些细胞因子的表达，从而支持 Cho 升高的神经炎症假说。
18 只野生型雄性 Wistar 大鼠中的 10 只（基线时体重约为 322 g）接受 EtOH 暴露，在 4 天内平均血液酒精水平达到约 315 mg/dl。在基线时、接受 5 次 EtOH （ binge ）后以及最后一次 EtOH 给药后 4 或 24 小时立即采集用于细胞因子免疫测定的血液。还测定了血液中硫胺素和肝酶的水平；死后进行了肝组织病理学检查；并测定了 6 个脑区的组织中 7 种细胞因子的潜在诱导情况。
硫胺素及其磷酸衍生物、单磷酸硫胺素和二磷酸硫胺素的水平没有组间差异。肝酶水平的 ANOVA 分析表明，只有 EtOH 组的碱性磷酸酶（ALP）水平在 binge 时高于对照组；然而，在没有其他肝酶水平变化的情况下，ALP 的升高很难解释。EtOH 组的死后肝组织病理学检查结果显示存在微小的微泡脂肪变性和门腔纤维性变。血液中测量的细胞因子（TNF-α、IFN-γ、IL-1β、IL-4、IL-5、IL-13 和 GRO/CXCL1）水平的组间差异无统计学意义。同样，死后对肝细胞因子的评估也没有发现组间差异。对 6 个脑区（小脑前蚓部、扣带回皮质、额叶皮质、海马体、下丘脑、纹状体）中 7 种细胞因子的死后评估也未能确定组间差异。
单次 4 天 binge EtOH 暴露不足以诱导野生型 Wistar 大鼠血液、肝脏或 6 个脑区中 7 种细胞因子的表达。因此，需要对 4 天 binge EtOH 治疗后大脑 Cho 升高的其他解释，包括未在此处测量的细胞因子的诱导或其他非炎症机制。
