[TLR4/MyD88/NF-κB通路基因及其相关炎症因子在继发性脊髓损伤中的表达]
[Expression of TLR4/MyD88/NF-κB pathway genes and its related inflammatory factors in secondary spinal cord injury].
作者信息
Mi Shuang, Wu Yanjun, Hong Zhenghua, Wang Zhangfu, Feng Xingbing, Zheng Guangbin
机构信息
Department of Spinal Surgery, Taizhou Hospital of Zhejiang Province, Taizhou 317000, Zhejiang Province, China.
出版信息
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2019 Dec 25;48(6):609-616. doi: 10.3785/j.issn.1008-9292.2019.12.04.
OBJECTIVE
To investigate the expression of Toll-like receptor 4 (TLR4)/myeloid differentiation factor (MyD88)/nuclear factor-κB (NF-κB) pathway genes and related inflammatory factors tumor necrosis factor-α (TNF-α), interleukin (IL)-12, IL-6 in patients with secondary spinal cord injury (SSCI) and the correlations with prognosis.
METHODS
The clinical data of 105 SSCI patients and 40 healthy subjects were reviewed. According to Frankel's classification of spinal cord injury, the patients were divided into complete injury group and incomplete injury group, and according to the improvement of Japanese Orthopedic Association (JOA) scores, the patients were divided into good prognosis group and poor prognosis group. The expression of TLR4, MyD88, NF-κB in peripheral blood mononuclear cells (PBMC) and serum TNF-α, IL-12, IL-6 levels were compared between SSCI patients and healthy controls, between patients with complete and incomplete injury, between patients with poor and good prognosis. Logistic regression analysis was used to analyze the risk factors leading to poor prognosis of SSCI, and Pearson's correlation analysis was used to analyze the correlation between JOA score and the above indicators.
RESULTS
The expressions of TLR4, MyD88, NF-κB in PBMC and serum TNF-α, IL-12, IL-6 levels in SSCI patients were significantly higher than those in healthy subjects (all <0.01), those in complete injury group were higher than those in incomplete injury group, and those in poor prognosis group were higher than those in good prognosis group (all <0.01). The proportions of patients with Frankel grade A, spinal cord edema or hemorrhage, spinal cord injury length longer than 4 cm in poor prognosis group was significantly higher than those in good prognosis group (all <0.01). Logistic regression analysis showed that Frankel grade, spinal cord edema or hemorrhage, length of spinal cord injury, relative expressions of TLR4, MyD88, NF-κB in PBMC, serum levels of TNF-α, IL-12 and IL-6 were risk factors for poor prognosis in SSCI patients (<0.05 or <0.01). Pearson's correlation analysis showed that JOA improvement rate was negatively correlated with the relative expressions of TLR4, MyD88, NF-κB mRNA in PBMC and serum TNF-α, IL-12, IL-6 levels (<0.05 or <0.01).
CONCLUSIONS
The activation of TLR4/MyD88/NF-κB pathway and the up-regulation of the expression of related inflammatory factors TNF-α, IL-12 and IL-6 are involved in the progression of SSCI, which are closely related to the neuroinflammatory injury, and can be used as reference indexes for evaluating prognosis in SSCI patients.
目的
探讨继发性脊髓损伤（SSCI）患者Toll样受体4（TLR4）/髓样分化因子（MyD88）/核因子-κB（NF-κB）通路基因及相关炎性因子肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-12、IL-6的表达情况及其与预后的相关性。
方法
回顾性分析105例SSCI患者和40例健康受试者的临床资料。根据Frankel脊髓损伤分级，将患者分为完全损伤组和不完全损伤组；根据日本骨科协会（JOA）评分改善情况，将患者分为预后良好组和预后不良组。比较SSCI患者与健康对照者、完全损伤与不完全损伤患者、预后不良与预后良好患者外周血单个核细胞（PBMC）中TLR4、MyD88、NF-κB的表达及血清TNF-α、IL-12、IL-6水平。采用Logistic回归分析SSCI患者预后不良的危险因素，采用Pearson相关分析JOA评分与上述指标的相关性。
结果
SSCI患者PBMC中TLR4、MyD88、NF-κB的表达及血清TNF-α、IL-12、IL-6水平均显著高于健康受试者（均P<0.01），完全损伤组高于不完全损伤组，预后不良组高于预后良好组（均P<0.01）。预后不良组Frankel A级、脊髓水肿或出血、脊髓损伤长度>4 cm患者的比例显著高于预后良好组（均P<0.01）。Logistic回归分析显示，Frankel分级、脊髓水肿或出血、脊髓损伤长度、PBMC中TLR4、MyD88、NF-κB的相对表达、血清TNF-α、IL-12及IL-6水平是SSCI患者预后不良的危险因素（P<0.05或P<0.01）。Pearson相关分析显示，JOA改善率与PBMC中TLR4、MyD88、NF-κB mRNA的相对表达及血清TNF-α、IL-12、IL-6水平呈负相关（P<0.05或P<0.01）。
结论
TLR4/MyD88/NF-κB通路的激活及相关炎性因子TNF-α、IL-12、IL-6表达上调参与了SSCI的进展，与神经炎性损伤密切相关，可作为评估SSCI患者预后的参考指标。
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