De La Cruz J P, Guerrero A, González-Correa J A, Arrebola M M, Sánchez de la Cuesta F
Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Málaga, Spain.
J Neurosci Res. 2004 Jan 15;75(2):280-290. doi: 10.1002/jnr.10851.
Acetylsalicylic acid (ASA) reduces the incidence of ischemic stroke mainly through its antithrombotic action; however, it also has a direct neuroprotective effect. The present study was designed to evaluate the effect of ASA on oxidative stress and the activity of nitric oxide synthase (NOS) in an in vitro model of hypoxia in rat brain slices. Rat brain slices were perfused with nitrogen (hypoxia) for a maximum of 120 min, after which we measured lipid peroxidation, glutathione levels, glutathione-related enzyme activities, and constitutive nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) activities. In brain tissue subjected to hypoxia, ASA reduced oxidative stress and iNOS activity (all increased by hypoxia), but only when used at higher concentrations. The effects of salicylic acid (SA) were similar but more intense than were those of ASA. After oral administration, the effect of SA was much greater than that of ASA, and the decrease in cell death with SA was seen much more clearly. In view of the greater effect of SA compared to ASA on changes in oxidative stress parameters in a model of hypoxia, and higher brain concentrations of SA when it is administered alone than when ASA is given (undetectable levels), we conclude that SA plays an important role in the cytoprotective effect in brain tissue after ASA administration.
乙酰水杨酸（ASA）主要通过其抗血栓作用降低缺血性中风的发生率；然而，它也具有直接的神经保护作用。本研究旨在评估ASA对大鼠脑片缺氧体外模型中氧化应激和一氧化氮合酶（NOS）活性的影响。将大鼠脑片用氮气灌注（缺氧）最长120分钟，之后我们测量脂质过氧化、谷胱甘肽水平、谷胱甘肽相关酶活性以及组成型一氧化氮合酶（cNOS）和诱导型一氧化氮合酶（iNOS）活性。在缺氧的脑组织中，ASA降低了氧化应激和iNOS活性（两者均因缺氧而增加），但仅在较高浓度使用时才有效。水杨酸（SA）的作用与之相似，但比ASA更强烈。口服给药后，SA的效果比ASA大得多，且SA导致的细胞死亡减少更为明显。鉴于在缺氧模型中SA相较于ASA对氧化应激参数变化的影响更大，且单独给药时SA在脑中的浓度高于ASA给药时（ASA浓度检测不到），我们得出结论，SA在ASA给药后脑组织的细胞保护作用中发挥重要作用。
