Interleukin-1β accelerates the onset of stroke in stroke-prone spontaneously hypertensive rats.

Interleukin-1β accelerates the onset of stroke in stroke-prone spontaneously hypertensive rats.
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DOI:
10.1155/2012/701976
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发表时间:
2012
影响因子:
4.6
通讯作者:
Satou T
Satou T
中科院分区:
医学3区
文献类型:
--
作者:
Chiba T;Itoh T;Tabuchi M;Nakazawa T;Satou T

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卒中病变中高水平的炎性生物标志物和免疫细胞已被认为是卒中的结果。然而,最近的研究表明,炎症发生在中风发病之前。在这项研究中,我们旨在阐明炎症在卒中易感自发性高血压大鼠(SHRSP)卒中发病中的作用。在4周龄(卒中前),自发性高血压大鼠(SHR)血浆IL-1β水平(153.0±49.7 pg/ml)显著高于Wistar京都大鼠(7.7±3.4 pg/ml,P<0.001)和自发性高血压大鼠(28.0±9.1 pg/ml,P&lt;0.001 vs SHRSP)(n=6)。自发性高血压大鼠脑血管内皮细胞也可见刺激的IL-1β信号。与免疫细胞募集相关的IL-1β、IL-1受体、半胱氨酸天冬氨酸氨基转移酶-1及其下游基因(单核细胞趋化蛋白-1和细胞间黏附分子-1)的基因表达在自发性高血压大鼠显著高于自发性高血压大鼠和自发性高血压大鼠,这与自发性高血压大鼠和自发性高血压大鼠比较,其核转录因子κB蛋白的表达水平更高。此外,使用渗透压泵持续给予IL-1β(2 μg/d)可使自发性高血压大鼠卒中的发生率略有增加(P=0.046),与对照组(每组10只)相比,自发性高血压大鼠卒中的发病明显加快(P=0.006)。这些结果表明,当伴有严重高血压时,刺激的IL-1β信号可能是卒中发病的原因之一。
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.
缺血性中风和心肌梗塞患者中MCP-1趋化因子的血清水平。
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