高压氧干预通过调节HMGB1/TLR4/NF-κB信号通路减轻大鼠继发性脊髓损伤。
Hyperbaric oxygen intervention reduces secondary spinal cord injury in rats via regulation of HMGB1/TLR4/NF-κB signaling pathway.
作者信息
Kang Nan, Hai Yong, Yang Jing, Liang Fang, Gao Chun-Jin
机构信息
Department of Orthopaedics, Beijing Chao-Yang Hospital, Capital Medical University Beijing 100020, P.R. China.
Department of Hyperbaric Oxygen, Beijing Chao-Yang Hospital, Capital Medical University Beijing 100020, P.R. China.
出版信息
Int J Clin Exp Pathol. 2015 Feb 1;8(2):1141-53. eCollection 2015.
BACKGROUND
To investigate whether hyperbaric oxygen (HBO) intervention affects the expressions of inflammatory cytokines, HMGB1/TLR4/NF-κB, and arrests secondary spinal cord injury (SCI).
METHODS
One hundred and twenty healthy adult SD rats were randomly divided into four groups: sham, sham + HBO, SCI, and SCI + HBO. Each group was then randomly divided into five subgroups of 6 rats each according to the following time points: 1, 2, 3, 7, and 14 d post injury. Functional recovery of the hindlimb was assessed by Basso, Beattie, and Bresnahan (BBB) scores at different time points after SCI. The expression of HMGB1, TLR4, and NF-κB in the spinal cord tissue was determined by fluorescence quantitative PCR, western blot, immunohistochemistry, and ELISA.
RESULTS
The gene expressions of TLR4, HMGB1, and NF-κB (P < 0.01) and the TLR4 protein expression were significantly high after SCI. HBO intervention significantly decreased all the four parameters at 3, 7, and 14 d post injury (P < 0.05). A significant positive correlation (P < 0.01) was observed between the following: HMGB1 mRNA, TLR4 mRNA and TLR4 protein; HMGB1 mRNA and NF-κB mRNA; and TLR4 protein and NF-κB mRNA. BBB score was negatively correlated with HMGB1, TLR4 protein and NF-κB levels. HBO intervention significantly improved the BBB scores at 7 and 14 d post injury (P < 0.05).
CONCLUSIONS
Hyperbaric oxygen reduced the expressions of HMGB1, TLR4, and NF-κB and reduced secondary SCI as measured using BBB scores.
背景
探讨高压氧（HBO）干预是否影响炎性细胞因子、HMGB1/TLR4/NF-κB的表达，并阻止继发性脊髓损伤（SCI）。
方法
将120只健康成年SD大鼠随机分为四组：假手术组、假手术+HBO组、SCI组和SCI+HBO组。然后根据损伤后1、2、3、7和14天这几个时间点，将每组随机分为五个亚组，每组6只大鼠。在SCI后的不同时间点，通过Basso、Beattie和Bresnahan（BBB）评分评估后肢的功能恢复情况。采用荧光定量PCR、蛋白质免疫印迹、免疫组织化学和酶联免疫吸附测定法检测脊髓组织中HMGB1、TLR4和NF-κB的表达。
结果
SCI后TLR4、HMGB1和NF-κB的基因表达（P<0.01）以及TLR4蛋白表达显著升高。HBO干预在损伤后3、7和14天显著降低了所有这四个参数（P<0.05）。观察到以下指标之间存在显著正相关（P<0.01）：HMGB1 mRNA、TLR4 mRNA与TLR4蛋白；HMGB1 mRNA与NF-κB mRNA；以及TLR4蛋白与NF-κB mRNA。BBB评分与HMGB1、TLR4蛋白和NF-κB水平呈负相关。HBO干预在损伤后7和14天显著提高了BBB评分（P<0.05）。
结论
高压氧降低了HMGB1、TLR4和NF-κB的表达，并减少了用BBB评分衡量的继发性SCI。
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