目的 分析脊柱结核术后Toll样受体（TLR）-4、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、IL-17的变化及与预后的相关性。方法 选择2021年1月—2022年12月收治的60例接受手术治疗的脊柱结核患者作为观察组,另选60例非脊柱结核且行脊柱手术的患者作为对照组（部分病例由基金项目中合作医院提供）。检测两组患者血清及病灶组织TLR-4、TNF-α、IL-6、IL-17表达水平。根据观察组患者术后6个月的预后情况,分为预后良好组和预后不良组,比较两组术前及术后6个月的血清TLR-4、TNF-α、IL-6、IL-17表达水平,使用Pearson相关性分析评价脊柱结核患者术前血清TLR-4、TNF-α、IL-6、IL-17表达水平与术后6个月改良巴氏指数（MBI）量表评分的关系,受试者工作特征（ROC）曲线分析术后血清TLR-4、TNF-α、IL-6联合IL-17对脊柱结核术后预后不良的预测效能。结果 观察组术前血清及病灶组织的TLR-4、TNF-α、IL-6、IL-17表达水平均高于对照组,差异均有统计学意义（P<0.05）;预后不良组术前血清TLR-4、TNF-α、IL-6、IL-17表达水平均高于预后良好组,差异均有统计学意义（P<0.05）;术后6个月,预后良好组血清TLR-4、TNF-α、IL-6、IL-17表达水平较术前明显降低,与预后不良组比较,差异均有统计学意义（P<0.05）;经Pearson相关性分析,脊柱结核患者术前血清TLR-4、TNF-α、IL-6、IL-17表达水平与术后6个月MBI量表评分呈负相关（P<0.05）;经ROC曲线分析,术前血清TLR-4、TNF-α、IL-6联合IL-17预测脊柱结核术后预后不良的ROC曲线下面积为0.921。结论 脊柱结核术后血清TLR-4、TNF-α、IL-6、IL-17较术前明显降低,与预后密切相关,术前血清TLR-4、TNF-α、IL-6联合IL-17预测预后不良的效能较好,值得临床予以重视。
Objective To analyze the changes of Toll-like receptor （TLR）-4, tumor necrosis factor （TNF）-α, interleukin （IL）-6, and IL-17 after spinal tuberculosis surgery and their correlations with prognosis. Methods Sixty patients with spinal tuberculosis who received surgical treatment in our hospital from January 2021 to December 2022 were selected as the observation group, and 60 patients without spinal tuberculosis who underwent spinal surgery were selected as the control group （Some cases were from partner hospitals in the Fund）. The expression levels of TLR-4, TNF-α, IL-6, and IL-17 in serum and lesion tissues of the two groups were detected. According to the prognosis 6 months after operation, patients in the observation group were divided into a good prognosis group and a poor prognosis group. Serum expression levels of TLR-4, TNF-α, IL-6, and IL-17 were compared between the two groups before and 6 months after operation. Pearson correlation was used to analyze the relationships between the expression levels of serum TLR-4, TNF-α, IL-6, and IL-17 before surgery and the score of modified Babbitt index （MBI） 6 months after surgery in patients with spinal tuberculosis. Receiver operating characteristic （ROC） curve was used to analyze the predictive efficacy of serum TLR-4, TNF-α, and IL-6 combined with IL-17 for postoperative poor prognosis of spinal tuberculosis. Results The expression levels of TLR-4, TNF-α, IL-6, and IL-17 in serum and lesion tissues of the observation group were higher than those of the control group before operation, with significant differences （P<0.05）. The levels of TLR-4, TNF-α, IL-6, and IL-17 in the poor prognosis group were higher than those in the good prognosis group,with significant differences （P<0.05）. Six months after surgery, the expression levels of TLR-4, TNF-α, IL-6, and IL-17 in serum of the good prognosis group were significantly lower than those before surgery, and the differences were statistically significant compared with those of the poor prognosis group （P<0.05）. By Pearson correlation analysis, the expression levels of serum TLR-4,TNF-α, IL-6, and IL-17 in patients with spinal tuberculosis before surgery were negatively correlated with MBI scale score 6 months after surgery （P<0.05）. According to ROC curve analysis, the area under curve of preoperative serum TLR-4, TNF-α, and IL-6 combined with IL-17 for predicting poor prognosis after spinal tuberculosis surgery was 0.921. Conclusion Serum TLR-4, TNF-α, IL-6, and IL-17 after spinal tuberculosis surgery are significantly lower than those before surgery, which is closely related to prognosis. Preoperative serum TLR-4, TNF-α, and IL-6 combined with IL-17 can predict poor prognosis effectively, which is worthy of clinical attention.
[1] 韩波波,姚超.160例脊柱结核患者临床特征分析[J].安徽医学,2021,42(12):1407-1410.
[2] 麦叶,林瑶瑶,刘海林,等.结核分枝杆菌对miR-21和TLR-4/NF-κB信号通路的影响研究[J].重庆医学,2021,50(3):367-371.
[3] Saghazadeh A, Rezaei N.Central inflammatory cytokines in tuberculous meningitis: a systematic review and meta-analysis[J].J Interferon Cytokine Res, 2022, 42(3): 95-107.
[4] Adankwah E, Nausch N, Minadzi D, et al.Interleukin-6 and Mycobacterium tuberculosis dormancy antigens improve diagnosis of tuberculosis[J]. J Infect, 2021, 82(2): 245-252.
[5] Nogueira M, Warren RB, Torres T.Risk of tuberculosis reactivation with interleukin (IL)-17 and IL-23 inhibitors in psoriasis-time for a paradigm change[J]. J Eur Acad Dermatol Venereol, 2021, 35(4): 824-834.
[6] 中华医学会结核病分会骨科专业委员会.中国脊柱结核外科治疗指南(2022年版)[J].中国矫形外科杂志,2022,30(17):1537-1548.
[7] 莫森,刘冲,陈立艺,等.外周血淋巴细胞circRNA在脊柱结核患者中表达的初步筛选及功能分析[J].广西医科大学学报,2019,36(5):749-754.
[8] Gupta A, Sharma K, Sharma V, et al.Comparative evaluation of interleukin-10,transforming growth factor-β,and interleukin-17 in gastrointestinal tuberculosis and Crohn's disease[J]. Int J Mycobacteriol, 2022, 11(4): 384-388.
[9] Agustin H, Massi MN, Djaharuddin I, et al.Correlation expression Toll-like receptor 4 with multidrugs resistant tuberculosis in diabetes mellitus condition[J]. Indian J Tuberc,2023, 70(1): 59-64.
[10] 史春光,郭润栋,安慧霞,等.血清MMP-2、TNF-α及IL-17在脊柱结核患者预后中的价值研究[J].颈腰痛杂志,2019,40(6):766-769.
[11] Jong RM, Van Dis E, Berry SB, et al.Mucosal vaccination with cyclic dinucleotide adjuvants induces effective T cell homing and IL-17-dependent protection against Mycobacterium tuberculosis infection[J]. J Immunol, 2022, 208(2): 407-419.
[12] 赵涛,梁亚萍,高腾飞,等.经第12肋骨前路病灶清除自体髂骨植骨融合钢板螺钉内固定术治疗胸腰段脊柱结核临床研究[J].陕西医学杂志,2019,48(11):1481-1484.
[13] Logesh R, Lavanya V, Jamal S, et al.Designing of a chimeric vaccine using EIS (Rv2416c) protein against Mycobacterium tuberculosis H37Rv: an immunoinformatics approach[J]. Appl Biochem Biotechnol, 2022, 194(1): 187-214.
[14] 李树根,冯大雄,汪在德,等.脊柱结核患者外周血TLR4、IL-17、Tollip mRNA水平及临床意义[J].临床误诊误治,2022,35(8):66-69.
[15] Ritter K, Behrends J, Erdmann H, et al.Interleukin-23 instructs protective multifunctional CD4 T cell responses after immunization with the Mycobacterium tuberculosis subunit vaccine H1 DDA/TDB independently of interleukin-17A[J]. J Mol Med (Berl), 2021, 99(11): 1585-1602.
[16] 李邦银,蒲育,何敏,等.脊柱结核术后未愈的影响因素分析[J].中国防痨杂志,2019,41(5):510-514.
[17] 刘姣,曲崇正,谢平金,等.膝骨性关节炎模型大鼠接受推拿治疗后软骨Toll样受体4/髓样分化因子88信号转导通路的变化[J].中国组织工程研究,2019,23(19):3019-3024.
[18] Faust HJ, Zhang H, Han J, et al.IL-17 and immunologically induced senescence regulate response to injury in osteoarthritis[J]. J Clin Invest, 2020, 130(10): 5493-5507.
