Tewari S, Diano M, Bera R, Nguyen Q, Parekh H
Department of Psychiatry and Human Behavior, California College of Medicine, University of California, irvine 92717.
Alcohol Clin Exp Res. 1992 Jun;16(3):436-42. doi: 10.1111/j.1530-0277.1992.tb01396.x.
The long-term effects of prenatal ethanol exposure on the properties of brain polysomes and the proliferative responses of lymphocytes to mitogenic stimulation in adult offspring were assessed. Female Sprague-Dawley rats either ingested the control or 6.6% ethanol-containing Lieber-DeCarli liquid diet during the 3rd trimester of pregnancy. Controls were age-matched and pair-fed. At 42 to 72 days of age, ethanol effects were evaluated on the (1) polysomal properties in the cerebral hemispheres, cerebellum, and hippocampal regions of the brain after translation in a messenger RNA (mRNA)-dependent rabbit reticulocyte lysate system and (2) immunologic functions of lymphocytes cultured from spleen cells by measuring their responses to mitogenic stimulation. Results showed long-term adverse effects of in utero ethanol exposure on the polysomal RNA translation in each of the three brain regions tested with free polysomal mRNAs affected more than the bound polysomal mRNAs. Of these, the hippocampal region appeared to sustain the most injurious effects. In addition, a suppression of the mitogen-induced lymphocyte proliferative responses were present under these conditions. The degree of suppression varied with the specific mitogen used. Data suggest that the ethanol effects on the CNS and lymphocyte proliferation are most possibly irreversible, and in the case of the CNS, a post-translational modification by ethanol is indicated. The reduced lymphocyte responses are suggestive of a possible interference by ethanol of the synthesis of interleukin-2 (IL-2) and/or a reduced binding of IL-2 with its receptor (IL-2 receptors).
评估了产前乙醇暴露对成年后代脑多核糖体特性以及淋巴细胞对有丝分裂原刺激的增殖反应的长期影响。雌性Sprague-Dawley大鼠在孕期的第三个月摄入对照或含6.6%乙醇的Lieber-DeCarli液体饮食。对照组为年龄匹配且配对喂养。在42至72日龄时,评估乙醇对以下方面的影响:(1) 在依赖信使核糖核酸(mRNA)的兔网织红细胞裂解物系统中进行翻译后,对大脑半球、小脑和海马区的多核糖体特性的影响;(2) 通过测量脾细胞培养的淋巴细胞对有丝分裂原刺激的反应,评估其免疫功能。结果显示,子宫内乙醇暴露对所测试的三个脑区中的每一个的多核糖体RNA翻译都有长期不良影响,游离多核糖体mRNA比结合多核糖体mRNA受到的影响更大。其中,海马区似乎受到的损伤最大。此外,在这些条件下,有丝分裂原诱导的淋巴细胞增殖反应受到抑制。抑制程度因所用的特定有丝分裂原而异。数据表明,乙醇对中枢神经系统和淋巴细胞增殖的影响很可能是不可逆的,就中枢神经系统而言,表明乙醇有翻译后修饰作用。淋巴细胞反应的降低提示乙醇可能干扰白细胞介素-2(IL-2)的合成和/或降低IL-2与其受体(IL-2受体)的结合。