A Longitudinal Analysis of Circulating Stress-Related Proteins and Chronic Ethanol Self-Administration in Cynomolgus Macaques
A Longitudinal Analysis of Circulating Stress-Related Proteins and Chronic Ethanol Self-Administration in Cynomolgus Macaques
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DOI：
10.1111/j.1530-0277.2011.01685.x
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发表时间：
2012-06-01
影响因子：
3.2
通讯作者：
Grant, Kathleen A.
中科院分区：
文献类型：
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作者：
Helms, Christa M.;Messaoudi, Ilhem;Grant, Kathleen A.
背景：酒精中毒者内分泌和免疫功能改变，易患应激相关疾病。然而，对灵长类动物长期乙醇摄入对稳态机制的纵向分析并不完全。研究方法：血浆蛋白（n = 60; Luminex）和激素（促肾上腺皮质激素[ACTH];皮质醇）在成年雄性食蟹猴中重复测量（食蟹猴，n = 10）在32个月的实验方案期间，在基线时，在水和乙醇诱导期间（4%w/v水溶液）自我给药，4个月后和12个月后每天22小时同时接触乙醇和水。结果如下：在ACTH、皮质醇和45/60血浆蛋白中观察到显著变化：大多数（28/45）被抑制为乙醇自身给药的函数，8种蛋白升高，9种显示双相变化。皮质醇和促肾上腺皮质激素是最大的诱导过程中，这些激素和血浆蛋白之间的相关性在整个实验中各不相同。通路分析显示核因子？-活化B细胞轻链增强子（NF-？B）和Janus激酶（JAK）/信号转导子和转录激活子（STAT）作为乙醇对灵长类动物免疫相关蛋白的诱导作用的可能介质。结论：灵长类动物的慢性乙醇消耗导致NF-？B和STAT/JAK相关通路与内分泌活动改变相关。
Background: Alcoholics have alterations in endocrine and immune functions and increased susceptibility to stress-related disorders. A longitudinal analysis of chronic ethanol intake on homeostatic mechanisms is, however, incompletely characterized in primates. Methods: Plasma proteins (n = 60; Luminex) and hormones (adrenocorticotropic hormone [ACTH]; cortisol) were repeatedly measured in adult male cynomolgus monkeys (Macaca fascicularis, n = 10) during a 32-month experimental protocol at baseline, during induction of water and ethanol (4% w/v in water) self-administration, after 4 months, and after 12 months of 22-hour daily concurrent access to ethanol and water. Results: Significant changes were observed in ACTH, cortisol, and 45/60 plasma proteins: a majority (28/45) were suppressed as a function of ethanol self-administration, 8 proteins were elevated, and 9 showed biphasic changes. Cortisol and ACTH were greatest during induction, and correlations between these hormones and plasma proteins varied across the experiment. Pathway analyses implicated nuclear factor ?-light-chain-enhancer of activated B cells (NF-?B) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) as possible mediators of ethanol-induced effects on immune-related proteins in primates. Conclusions: Chronic ethanol consumption in primates leads to an allostatic state of physiological compromise with respect to circulating immune- and stress-related proteins in NF-?B- and STAT/JAK-related pathways in correlation with altered endocrine activity.