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损伤后黄芩苷可改善实验性创伤性脑损伤后的组织学和功能结果,并减少炎性细胞因子。

Post-injury baicalein improves histological and functional outcomes and reduces inflammatory cytokines after experimental traumatic brain injury.

作者信息

Chen S-F, Hsu C-W, Huang W-H, Wang J-Y

机构信息

Department of Physical Medicine and Rehabilitation, Cheng Hsin Rehabilitation Medical Center, Taipei, Taiwan, Republic of China.

出版信息

Br J Pharmacol. 2008 Dec;155(8):1279-96. doi: 10.1038/bjp.2008.345. Epub 2008 Sep 8.

Abstract

BACKGROUND AND PURPOSE

Traumatic brain injury (TBI) triggers a complex series of inflammatory responses that contribute to secondary tissue damage. The aim of this study was to investigate the effect of baicalein, a flavonoid possessing potent anti-inflammatory properties, on functional and histological outcomes and inflammatory cytokine expression, following TBI in rats.

EXPERIMENTAL APPROACH

Rats subjected to controlled cortical impact injury were injected with baicalein (30 mg kg(-1)) or vehicle immediately after injury or daily for 4 days. Neurological status was evaluated using the rotarod, adhesive removal, modified neurological severity scores and beam walk tests. Contusion volume and neuronal degeneration were measured using cresyl violet and FluoroJade B (FJB) histochemistry. Levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) mRNA and protein were assessed by real-time quantitative reverse transcriptase-PCR, enzyme-linked immunosorbent assay and immunohistochemistry.

KEY RESULTS

Single-dose and multiple-dose treatment with baicalein significantly improved functional recovery and reduced contusion volumes up to day 28 post-injury, although multiple-dose baicalein was the more effective treatment. Single-dose baicalein also significantly reduced the number of degenerating neurons (31%) on post-injury day 1 as indicated by FJB staining. These changes were associated with significantly decreased levels, at the contusion site, of TNF-alpha, IL-1 beta and IL-6 mRNA at 6 h, and cytokine protein on day 1 post-injury.

CONCLUSIONS AND IMPLICATIONS

Post-injury treatment with baicalein improved functional and histological outcomes and reduced induction of proinflammatory cytokines in rat TBI. The neuroprotective effect of baicalein may be related to a decreased inflammatory response following the injury.

摘要

背景与目的

创伤性脑损伤(TBI)引发一系列复杂的炎症反应,这些反应会导致继发性组织损伤。本研究的目的是探究黄芩素(一种具有强大抗炎特性的黄酮类化合物)对大鼠创伤性脑损伤后功能和组织学结果以及炎性细胞因子表达的影响。

实验方法

对遭受控制性皮质撞击损伤的大鼠,在损伤后立即注射黄芩素(30毫克/千克)或赋形剂,或连续4天每日注射。使用转棒试验、黏附去除试验、改良神经严重程度评分和横梁行走试验评估神经功能状态。使用甲酚紫和荧光金(FJB)组织化学测量挫伤体积和神经元变性。通过实时定量逆转录聚合酶链反应、酶联免疫吸附测定和免疫组织化学评估肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的mRNA和蛋白质水平。

主要结果

黄芩素单剂量和多剂量治疗均显著改善了功能恢复,并在损伤后28天内减小了挫伤体积,尽管多剂量黄芩素治疗效果更佳。FJB染色显示,单剂量黄芩素还显著减少了损伤后第1天变性神经元的数量(31%)。这些变化与损伤后6小时挫伤部位TNF-α、IL-1β和IL-6 mRNA水平以及损伤后第1天细胞因子蛋白水平的显著降低有关。

结论与意义

损伤后用黄芩素治疗可改善大鼠创伤性脑损伤的功能和组织学结果,并减少促炎细胞因子的诱导。黄芩素的神经保护作用可能与损伤后炎症反应的减少有关。

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