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细胞因子、伴侣蛋白与海洛因相关死亡的神经炎症反应:不同细胞表达模式能让我们了解什么?

Cytokines, chaperones and neuroinflammatory responses in heroin-related death: what can we learn from different patterns of cellular expression?

机构信息

Department of Forensic Pathology, University of Foggia, Ospedale Colonnello D'Avanzo, Viale degli Aviatori 1, Foggia 71100, Italy.

出版信息

Int J Mol Sci. 2013 Sep 30;14(10):19831-45. doi: 10.3390/ijms141019831.

DOI:10.3390/ijms141019831
PMID:24084728
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3821589/
Abstract

Heroin (3,6-diacetylmorphine) has various effects on the central nervous system with several neuropathological alterations including hypoxic-ischemic brain damage from respiratory depressing effects and neuroinflammatory response. Both of these mechanisms induce the release of cytokines, chemokines and other inflammatory mediators by the activation of many cell types such as leucocytes and endothelial and glial cells, especially microglia, the predominant immunocompetent cell type within the central nervous system. The aim of this study is to clarify the correlation between intravenous heroin administration in heroin related death and the neuroinflammatory response. We selected 45 cases among autopsies executed for heroin-related death (358 total cases); immunohistochemical studies and Western blotting analyses were used to investigate the expression of brain markers such as tumor necrosis factor-α, oxygen-regulated protein 150, (interleukins) IL-1β, IL-6, IL-8, IL-10, IL-15, cyclooxygenase-2, heat shock protein 70, and CD68 (MAC387). Findings demonstrated that morphine induces inflammatory response and cytokine release. In particular, oxygen-regulated protein 150, cyclooxygenase-2, heat shock protein 70, IL-6 and IL-15 cytokines were over-expressed with different patterns of cellular expression.

摘要

海洛因(3,6-二乙酰吗啡)对中枢神经系统有多种作用,包括呼吸抑制作用引起的缺氧缺血性脑损伤和神经炎症反应。这两种机制通过激活许多细胞类型,如白细胞、内皮细胞和神经胶质细胞,特别是小胶质细胞,中枢神经系统中主要的免疫活性细胞类型,引起细胞因子、趋化因子和其他炎症介质的释放。本研究旨在阐明静脉内海洛因给药与神经炎症反应在海洛因相关死亡中的相关性。我们在海洛因相关死亡的尸检中选择了 45 例(358 例总例数);免疫组织化学研究和 Western blot 分析用于研究脑标志物如肿瘤坏死因子-α、氧调节蛋白 150、(白细胞介素)IL-1β、IL-6、IL-8、IL-10、IL-15、环氧化酶-2、热休克蛋白 70 和 CD68(MAC387)的表达。研究结果表明,吗啡诱导炎症反应和细胞因子释放。特别是,氧调节蛋白 150、环氧化酶-2、热休克蛋白 70、IL-6 和 IL-15 细胞因子表达过度,细胞表达模式不同。

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