Enhanced expression of interleukin (IL)-1 and IL-6 messenger RNA and bioactive protein after hypoxia-ischemia in neonatal rats

Enhanced expression of interleukin (IL)-1 and IL-6 messenger RNA and bioactive protein after hypoxia-ischemia in neonatal rats
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DOI:
10.1203/00006450-199610000-00015
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发表时间:
1996-10-01
期刊:
影响因子:
3.6
通讯作者:
Soder, O
Soder, O
中科院分区:
医学3区
文献类型:
--
作者:
Hagberg, H;Gilland, E;Soder, O

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研究了缺氧缺血(HI)对白细胞介素 - 1(IL - 1)和白细胞介素 - 6(IL - 6)生物活性以及白细胞介素 - 1α、白细胞介素 - 1β和白细胞介素 - 6 mRNA表达的影响,并评估了白细胞介素 - 1受体拮抗剂(IL - 1ra)对新生大鼠的神经保护功效。通过单侧颈动脉结扎和缺氧70 - 100分钟的方法在7日龄大鼠中诱导HI。在HI后直至14天的不同时间点处死动物,使用生物测定法分析大脑中IL - 1和IL - 6的生物活性,并通过逆转录及随后的聚合酶链反应分析白细胞介素 - 1α、白细胞介素 - 1β和白细胞介素 - 6的mRNA。在另外的动物中,在HI之前或之后脑室内给予IL - 1ra,并在HI后14天评估脑损伤程度。HI后IL - 1生物活性出现短暂升高,在恢复6小时达到峰值。IL - 1β mRNA的变化时间进程相似,但在3小时达到最大表达。IL - 6生物活性和mRNA也受到HI的刺激,且时间进程与IL - 1相似。IL - 1ra预处理将HI脑损伤从54.4 ± 9.3%降低到41.4 ± 10.0%(p≤0.01),与溶媒处理的对照组(13%)相比,IL - 1ra后处理使无脑部损伤的动物比例增加(40%)(p≤0.05)。总之,HI后IL - 1和IL - 6出现短暂激活,IL - 1ra可在一定程度上减轻HI脑损伤。
The effect of hypoxia-ischemia (HI) on IL-1, and IL-6 bioactivity in relation to expression of IL-1 alpha, IL-1 beta, and IL-6 mRNA was studied, and the neuroprotective efficacy of IL-1 receptor antagonist (IL-1ra) was evaluated in neonatal rats, HI was induced in 7-d-old rats by unilateral carotid artery ligation and hypoxia for 70-100 min. Animals were killed at different time points up to 14 d after HI, and brains were analyzed for IL-1 and IL-6 bioactivity using bioassays and for mRNA for IL-1 alpha, IL-1 beta, and IL-6 with reverse transcription followed by a polymerase chain reaction. In separate animals, IL-1ra was administered intracerebrally before or after HI, and the extent of brain injury was assessed 14 d after HI. A transient increase of IL-1 bioactivity occurred after HI, reaching a peak at 6 h of recovery. IL-1 beta mRNA followed a similar time course but attained maximum expression at 3 h. IL-6 bioactivity and mRNA were also stimulated by HI and followed a similar time course as IL-1. Pretreatment with IL-1ra reduced HI brain damage from 54.4 +/- 9.3 to 41.4 +/- 10.0% (p less than or equal to 0.01), and IL-1ra posttreatment increased the proportion of animals devoid of brain injury (40%) compared with vehicle-treated controls (13%) (p less than or equal to 0.05). In conclusion, a transient activation of IL-1 and IL-6 occurred after HI, and IL-1ra reduced HI brain injury to a moderate degree.