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青春期大鼠间断性和连续性摄取乙醇:对垂体-性腺轴活动和垂体前叶氧化应激的 24 小时模式的影响。

Discontinuous versus continuous drinking of ethanol in peripubertal rats: effect on 24-hour pattern of hypophyseal-gonadal axis activity and anterior pituitary oxidative stress.

机构信息

Department of Biochemistry and Molecular Biology III, Universidad Complutense, Madrid, Spain.

出版信息

Neuroendocrinology. 2012;96(3):194-203. doi: 10.1159/000334963. Epub 2012 Jan 26.

Abstract

AIMS

Discontinuous (weekend) consumption of alcohol is common in adolescents and young adults. This study therefore assesses, in peripubertal male rats, the effect of discontinuous as compared to chronic feeding of ethanol or control liquid diet.

METHODS

Animals received an ethanol liquid diet (6.2 % w/v) starting on day 35 of life. Every week for 5 weeks, the discontinuous ethanol group received the ethanol diet for 3 consecutive days and the control liquid diet for 4 days. At the 5th week, 24 h after the last ethanol administration to the discontinuously ethanol-treated animals, rats were killed at 4-hour intervals beginning at 09.00 h. Chronically administered rats received the ethanol diet until immediately before study.

RESULTS

Disrupted 24-hour rhythmicity together with a significant nocturnal increase in plasma luteinizing hormone (LH), testosterone and prolactin (PRL) occurred in the discontinuous ethanol group. Plasma ethanol levels were undetectable at 24 h after the last ethanol treatment. In contrast, after chronic ethanol administration, plasma PRL was increased late in scotophase while LH and testosterone decreased; blood ethanol levels were 2-fold greater than those in discontinuously ethanol-administered rats killed immediately after ethanol withdrawal. Circulating testosterone positively correlated with LH levels in control rats only. Chronic administration of ethanol significantly augmented mean expression of pituitary nitric oxide synthase (NOS)-2, heme oxygenase (HO)-1, Per1 and Per2 genes and disrupted their diurnal rhythmicity. Decreased NOS-1 and NOS-2 expression during scotophase, together with suppression of the rhythm in Per1 and Per2 expression, were found in the discontinuous ethanol group.

CONCLUSIONS

Abstinence after discontinuous drinking of alcohol in rats, as compared to chronic administration of ethanol, is accompanied by increases of plasma LH and testosterone, a greater PRL response and a less pronounced oxidative damage of the anterior pituitary.

摘要

目的

青少年和年轻人中经常出现间断(周末)饮酒的情况。因此,本研究在青春期前雄性大鼠中评估了与慢性喂养乙醇或对照液体饮食相比,间断喂养乙醇的影响。

方法

动物从 35 天大开始接受乙醇液体饮食(6.2%w/v)。在 5 周的时间内,每周连续 3 天给予间断乙醇组乙醇饮食,连续 4 天给予对照液体饮食。在第 5 周,在间断乙醇处理动物最后一次给予乙醇后 24 小时,从 09.00 小时开始每隔 4 小时杀死一组大鼠。慢性给予乙醇的大鼠在研究前立即接受乙醇饮食。

结果

间断乙醇组出现 24 小时节律紊乱,并伴有明显的夜间促黄体激素(LH)、睾酮和催乳素(PRL)升高。最后一次乙醇处理后 24 小时,血浆乙醇水平无法检测到。相比之下,在慢性乙醇给药后,PRL 在暗期晚期升高,而 LH 和睾酮降低;血液乙醇水平是立即在乙醇戒断后处死的间断乙醇给药大鼠的两倍。在对照大鼠中,循环睾酮与 LH 水平呈正相关。慢性给予乙醇显著增加了垂体一氧化氮合酶(NOS)-2、血红素加氧酶(HO)-1、Per1 和 Per2 基因的平均表达,并破坏了它们的昼夜节律。在间断乙醇组中,暗期 NOS-1 和 NOS-2 表达减少,Per1 和 Per2 表达节律受到抑制。

结论

与慢性给予乙醇相比,大鼠间断饮酒后戒断时,血浆 LH 和睾酮增加,PRL 反应更大,前垂体的氧化损伤程度较轻。

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