Progesterone and allopregnanolone reduce inflammatory cytokines after traumatic brain injury
Progesterone and allopregnanolone reduce inflammatory cytokines after traumatic brain injury
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DOI：
10.1016/j.expneurol.2004.06.008
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发表时间：
2004-10-01
影响因子：
5.3
通讯作者：
Stein, DG
中科院分区：
文献类型：
--
作者：
He, J;Evans, CO;Stein, DG
创伤性脑损伤 (TBI) 后，白细胞介素 1β (IL-1β) 和肿瘤坏死因子 α (TNF-α) 的过度释放是脑水肿的主要原因，进而导致实验室大鼠永久性神经元丢失和认知缺陷。本研究检测了脑损伤大鼠在接受黄体酮 (8 mg/kg) 或四氢孕酮 (4 mg/kg) 治疗后，在损伤后 3、8、12 小时和 6 天时促炎细胞因子 IL-1β 和 TNF-α 表达的变化。成年雄性大鼠接受双侧前额皮质挫伤或假手术。激素在 1 小时和 6 小时腹腔注射，每天一次，持续长达 5 天。使用实时定量逆转录聚合酶链反应（RT-PCR）通过mRNA测量IL-1β和TNF-α的基因表达。使用酶联免疫吸附测定 (ELISA) 测量 IL-1β 和 TNF-α 的蛋白质浓度，以确认从 mRNA 到蛋白质的翻译。结果表明，黄体酮和四氢孕酮会在损伤后 3 小时（此时这些细胞因子的表达达到峰值）降低 IL-1β 和 TNF-α。损伤后 8 小时和 12 小时，与假手术组相比，受伤大鼠的 IL-1β 和 TNF-α 基因表达仍然升高。到损伤后第六天，细胞因子表达恢复到完整大鼠的水平。我们得出结论，孕酮和别孕酮可能会在 TBI 后早期减弱促炎细胞因子的产生，这可能是孕酮和别孕酮减轻脑水肿并促进 TBI 功能恢复的机制之一。 (C) 2004 Elsevier Inc. 保留所有权利。
Following a traumatic brain injury (TBI), the excessive release of interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) is a major cause of cerebral edema, which, in turn, can cause permanent neuronal loss and cognitive deficits in laboratory rats. This study examined the changes in expression of the proinflammatory cytokines IL-1beta and TNF-alpha after progesterone (8 mg/kg) or allopregnanolone (4 mg/kg) treatment in brain-injured rats at 3, 8, and 12 h and 6 days post-injury. Adult male rats received either bilateral prefrontal cortical contusion or sham surgery. The hormones were given intraperitoneally at 1 and 6 h, and continued once per day for up to 5 days. The gene expression of IL-1beta and TNF-alpha was measured by mRNA using real-time quantitative reverse transcripted polymerase chain reaction (RT-PCR). The protein concentrations of IL-1beta and TNF-alpha were measured using enzyme-linked immunosorbent assay (ELISA) to confirm the translation from mRNA to protein. The results indicated that progesterone and allopregnanolone reduce both IL-1beta and TNF-alpha at 3 h post-injury, when the expression of these cytokines peaks. At 8 and 12 h post-injury, IL-1beta and TNF-alpha gene expression in injured rats was still elevated compared to shams. By the sixth day post-injury, cytokine expression was back to the level of intact rats. We conclude that progesterone and allopregnanolone may attenuate the production of proinflammatory cytokines early after TBI, and this may be one mechanism by which progesterone and allopregnanolone reduce cerebral edema and promote functional recovery from TBI. (C) 2004 Elsevier Inc. All rights reserved.