Information Center, National Institute of Health and Nutrition, Shinjuku-ku, Tokyo, Japan.
Mediators Inflamm. 2012;2012:701976. doi: 10.1155/2012/701976. Epub 2012 Dec 27.
High blood levels of inflammatory biomarkers and immune cells in stroke lesions have been recognized as results of stroke. However, recent studies have suggested that inflammation occurs prior to stroke onset. In this study, we aimed to clarify the role of inflammation in stroke onset among stroke-prone spontaneously hypertensive rats (SHRSP). At 4 weeks of age (before stroke onset), the plasma level of IL-1β was significantly higher in SHRSP (153.0 ± 49.7 pg/ml) than in Wistar Kyoto rats (WKY) (7.7 ± 3.4 pg/ml, P < 0.001 versus SHRSP) or spontaneously hypertensive rats (SHR) (28.0 ± 9.1 pg/ml, P < 0.001 versus SHRSP) (n = 6 per strain). Stimulated IL-1β signal was also observed in cerebrovascular endothelial cells of SHRSP. Gene expressions of IL-1β, IL-1 receptors, caspase-1, and downstream genes (MCP-1 and ICAM-1), which associated with immune cell recruitment, were significantly greater in SHRSP than in WKY or SHR, coincident with greater NFκB protein levels in SHRSP compared to WKY or SHR. In addition, continuous administration of IL-1β (2 μg/day) using an osmotic pump slightly increased the incidence of stroke in SHR (P = 0.046) and significantly accelerated the onset of stroke in SHRSP (P = 0.006) compared to each control (n = 10 per group). These results suggest that a stimulated IL-1β signal might be a cause of stroke onset when concomitant with severe hypertension.
血液中炎症生物标志物和免疫细胞水平升高已被认为是中风的结果。然而，最近的研究表明，炎症发生在中风发作之前。在这项研究中，我们旨在阐明炎症在易发生中风的自发性高血压大鼠（SHRSP）中风发作中的作用。在 4 周龄（中风发作前），SHRSP 的血浆白细胞介素-1β（IL-1β）水平明显高于 Wistar Kyoto 大鼠（WKY）（7.7 ± 3.4 pg/ml，P < 0.001 与 SHRSP 相比）或自发性高血压大鼠（SHR）（28.0 ± 9.1 pg/ml，P < 0.001 与 SHRSP 相比）（每组 6 只）。在 SHRSP 的脑血管内皮细胞中也观察到了受刺激的 IL-1β信号。IL-1β、IL-1 受体、半胱天冬酶-1 和下游基因（MCP-1 和 ICAM-1）的基因表达在 SHRSP 中明显高于 WKY 或 SHR，与 SHRSP 中 NFκB 蛋白水平高于 WKY 或 SHR 相一致。此外，通过渗透泵持续给予 2 μg/天的 IL-1β 略微增加了 SHR 中风的发生率（P = 0.046），并明显加速了 SHRSP 中风的发作（P = 0.006），与每组对照相比（每组 10 只）。这些结果表明，当与严重高血压同时存在时，受刺激的 IL-1β 信号可能是中风发作的原因。
