Peroulis Nikos, Kourounakis Angeliki P, Yiangou Minas, Paramythiotis Daniel, Kotzampassi Katerina, Hadjipetrou Lygeri
Department of Genetics, Development and Molecular Biology, School of Biology, Faculty of Sciences, Aristotelian University of Thessaloniki, Thessaloniki, Greece.
Arzneimittelforschung. 2006;56(10):688-94. doi: 10.1055/s-0031-1296774.
Ischaemia-reperfusion injury is associated with an inflammatory response as well as apoptosis in the affected area. Inflammatory responses are characterized, among others, by an increased production of several cytokines, while caspases are implicated in the control of apoptosis. The aim of the present work was to determine changes in the levels of inflammatory and apoptotic indices in the rat brain after cerebral ischaemia-reperfusion and to evaluate the effect of the non-steroidal anti-inflammatory compound N-(2-thiolethyl)-2-{2-[N'-[2,6-dichlorophenyl)aminolphenyl} acetamide on these indices. A cerebral ischaemia-reperfusion rodent model was used to investigate, via immunohistochemical and colorimetric techniques, the presence in the brain and spleen of inflammatory enzymes cycloxygenases COX-1 and COX-2, cytokines interleukin (IL)-1beta, IL-4, IL-6, IL-10, IL-18, tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) as well as the activated form of caspase-3, in treated and untreated animals. Cerebral ischaemia-reperfusion caused elevated levels in the rat post ischaemia. Treatment with the antiinflammatory derivative reduced the elevation, caused by ischaemia, of IFN-gamma, TNF-alpha, IL-1beta IL-6, IL-18 and caspase-3 levels at 3 days post ischaemia, while it increased the levels of IL-10. It was shown that the increase in concentrations of a wide range of cytokines involved in the inflammatory reaction causing brain damage after ischaemia-reperfusion can be partially reversed by the anti-inflammatory derivative used in this study.
缺血再灌注损伤与受影响区域的炎症反应以及细胞凋亡有关。炎症反应的特征包括多种细胞因子的产生增加，而半胱天冬酶参与细胞凋亡的调控。本研究的目的是确定脑缺血再灌注后大鼠脑中炎症和凋亡指标水平的变化，并评估非甾体抗炎化合物N-(2-硫代乙基)-2-{2-[N'-[(2,6-二氯苯基)氨基]苯基}乙酰胺对这些指标的影响。使用脑缺血再灌注啮齿动物模型，通过免疫组织化学和比色技术，研究经处理和未经处理的动物大脑和脾脏中炎症酶环氧化酶COX-1和COX-2、细胞因子白细胞介素(IL)-1β、IL-4、IL-6、IL-10、IL-18、肿瘤坏死因子α(TNF-α)和干扰素γ(IFN-γ)以及活化形式的半胱天冬酶-3的存在情况。脑缺血再灌注导致大鼠缺血后这些指标水平升高。用抗炎衍生物治疗可降低缺血后3天时缺血引起的IFN-γ、TNF-α、IL-1β、IL-6、IL-18和半胱天冬酶-3水平的升高，同时提高IL-10水平。结果表明，本研究中使用的抗炎衍生物可部分逆转缺血再灌注后导致脑损伤的炎症反应中多种细胞因子浓度的升高。
