TLR4/MyD88/NF-κB通路基因及相关炎症因子在继发性脊髓损伤患者中的表达

Expression of TLR4/MyD88/NF-κB pathway genes and its related inflammatory factors in secondary spinal cord injury

目的:探讨Toll样受体4(TLR4)/髓样分化因子(MyD88)/NF-κB通路基因及相关炎症因子TNF-α、IL-12、IL-6在继发性脊髓损伤(SSCI)患者中的表达及与预后的相关性。方法:回顾性分析2017年7月至2018年6月浙江省台州医院收治的105例SSCI患者及40名健康体检者的临床资料。根据Frankel脊髓损伤分级评估结果将SSCI患者分为完全损伤组和不完全损伤组,根据日本矫形外科学会(JOA)患者神经功能改善率将SSCI患者分为预后优良组和预后不良组。对比SSCI患者与健康体检者、完全损伤组与不完全损伤组、预后优良组与预后不良组外周血单个核细胞(PBMC)中TLR4、MyD88、NF-κB mRNA表达及血清TNF-α、IL-12、IL-6水平;采用Logistic回归分析法分析导致SSCI患者预后不良的危险因素,并采用Pearson相关性分析法分析JOA改善率与上述指标的相关性。结果:SSCI患者PBMC中TLR4、MyD88、NF-κB mRNA表达量及血清TNF-α、IL-12、IL-6水平均高于健康体检者(均P<0.01),完全损伤组上述指标均高于不完全损伤组,且预后不良组高于预后优良组(均P<0.01)。预后不良组Frankel分级A级、脊髓水肿或出血、脊髓损伤长度超过4 cm患者的比例均高于预后优良组(均P<0.01),且经Logistic回归分析证实Frankel分级、脊髓水肿或出血、脊髓损伤长度及PBMC中TLR4、MyD88、NF-κB mRNA相对表达量、血清TNF-α、IL-12、IL-6水平均是导致SSCI患者预后不良的危险因素(P<0.05或P<0.01)。Pearson相关性分析结果显示,JOA改善率与PBMC中TLR4、MyD88、NF-κB mRNA相对表达量以及血清TNF-α、IL-12、IL-6水平均呈负相关(P<0.05或P<0.01)。结论:TLR4/MyD88/NF-κB通路激活及其相关炎症因子TNF-α、IL-12、IL-6表达上调参与SSCI疾病进展且与神经炎症损伤关系密切,可作为评估SSCI患者预后的参考指标。

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 P<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 P<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 P<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(P<0.05 or P<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(P<0.05 or P<0.01).Conclusion: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.