二十二碳六烯酸通过调节 TLR4/NF-κB 信号通路对大鼠创伤性脑损伤模型的神经保护作用。
Neuroprotective effect of docosahexaenoic acid in rat traumatic brain injury model via regulation of TLR4/NF-Kappa B signaling pathway.
机构信息
Department of Neurosurgery, Jinshan Hospital of Fudan University, Shanghai, 200540, China.
Department of Gastroenterology, Fuqing City Hospital of Fujian Province, Fuqing, 350300, Fujian, China.
出版信息
Int J Biochem Cell Biol. 2018 Jun;99:64-71. doi: 10.1016/j.biocel.2018.03.017. Epub 2018 Mar 27.
OBJECTIVE
The experiments were conducted to prove that docosahexaenoic acid (DHA) alleviates traumatic brain injury (TBI) through regulating TLR4/NF-Kappa B signaling pathway.
METHODS
Bioinformatic analysis was performed using published data from Gene Expression Omnibus (GEO) database to investigate differentially expressed genes and signaling pathways. Controlled cortical impact (CCI) injury rat model was built, and DHA (16 mg/kg in DMSO, once each day) was used to treat TBI rats. Neurological severity score (NSS) and beam walking test and rotarod test were used to confirm whether DHA is neuron-protective against TBI. The expression of TLR4, NF-Kappa B p65, (TNF)-α and IL-1β were examined by qRT-PCR and western blot. The impact of DHA on neurocyte apoptosis was validated by TdT-mediated dUTP Nick-End Labeling (TUNEL) staining. The influence of DHA on CD11b and GFAP expression in the hippocampus was determined through immunohistochemical analysis.
RESULTS
TLR4/NF Kappa B pathway was suggested to be closely correlated with TBI by bioinformatic analysis. DHA could improve the neurological function and learning and memory ability of rats after TBI as well as promote neurocytes from apoptosis. TLR4 expression and the expression of inflammatory mediator NF-Kappa B were also repressed by DHA treatment.
CONCLUSIONS
DHA exerted a neuron-protective influence in a rat model of TBI via repressing TLR4/NF-Kappa B pathway.
目的
实验旨在通过调节 TLR4/NF-κB 信号通路证明二十二碳六烯酸（DHA）缓解创伤性脑损伤（TBI）。
方法
使用基因表达综合数据库（GEO）中已发表的数据进行生物信息学分析，以研究差异表达基因和信号通路。建立控制性皮质撞击（CCI）损伤大鼠模型，并用 DHA（DMSO 中的 16mg/kg，每天一次）治疗 TBI 大鼠。神经功能严重程度评分（NSS）、束状行走试验和转棒试验用于确认 DHA 是否对 TBI 具有神经元保护作用。通过 qRT-PCR 和 Western blot 检测 TLR4、NF-κB p65、（TNF）-α 和 IL-1β的表达。通过 TdT 介导的 dUTP 缺口末端标记（TUNEL）染色验证 DHA 对神经细胞凋亡的影响。通过免疫组织化学分析确定 DHA 对海马中 CD11b 和 GFAP 表达的影响。
结果
生物信息学分析表明 TLR4/NF-κB 通路与 TBI 密切相关。DHA 可改善 TBI 后大鼠的神经功能和学习记忆能力，促进神经细胞凋亡。DHA 处理还抑制 TLR4 表达和炎症介质 NF-κB 的表达。
结论
DHA 通过抑制 TLR4/NF-κB 通路对 TBI 大鼠发挥神经元保护作用。
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