脊柱结核患者血清中炎性因子、MMPs水平及其与预后的关系

Levels of serum inflammatory factors and MMPs in patients with spinal tuberculosis and their relationship with prognosis

目的检测肿瘤坏死因子(TNF)-α、白介素(IL)-6、IL-10、基质金属蛋白酶(MMP)2、MMP9在脊柱结核患者血清中的水平并探讨它们与预后的关系。方法选取2015年7月至2017年4月确诊的脊柱结核患者63例为研究对象(脊柱结核组),选取同期健康体检者36例作为对照组。分别抽取对照组清晨空腹及脊柱结核组术前空腹肘静脉血,采用酶联免疫吸附(ELISA)法检测血清TNF-α、IL-6、IL-10水平,Western blot法检测血清MMP2、MMP9蛋白表达水平,采用改良巴氏指数(MBI)评估脊柱结核组患者预后情况。结果脊柱结核患者血清TNF-α、IL-6水平及MMP2、MMP9蛋白表达水平高于对照组(P均<0.01),IL-10水平低于对照组(P<0.01)。不同症状持续时间(除MMP2、MMP9外)、疼痛强度、血沉、C-反应蛋白水平的脊柱结核患者,其血清TNF-α、IL-6、IL-10、MMP2、MMP9水平比较,差异均有统计学意义(P均<0.01)。脊柱结核预后良好组(n=28)患者TNF-α、IL-6、MMP2、MMP9水平显著低于预后不良组(n=35)(P均<0.01),IL-10水平高于预后不良组(P<0.01)。MBI与TNF-α、IL-6、MMP9水平呈正相关(P<0.01,P<0.05);与IL-10水平呈负相关(P<0.01);与MMP2水平无明显相关性(P>0.05)。绘制ROC曲线发现,不良预后与血清中较高TNF-α、IL-6、MMP9水平密切相关;良好预后与较高IL-10水平密切相关。结论 TNF-α、IL-6、MMP2、MMP9在脊柱结核患者血清中水平明显增高,IL-10水平明显降低,有望成为判断脊柱结核预后的有效生物标志物。

Objective To detect the levels of serum tumor necrosis factor（TNF）-α,interleukin（IL）-6,IL-10,matrix metalloproteinase（MMP） 2 and MMP9 in patients with spinal tuberculosis and explore their relationship with prognosis.Methods Sixty-three diagnosed spinal tuberculosis patients from July 2015 to April 2017 were selected as the research objects（spinal tuberculosis group）,and 36 healthy subjects at the same time were selected as control group. Fasting elbow vein blood in the morning for control group and in the pre-operation for spinal tuberculosis group were extracted. Enzyme linked immunosorbent assay（ELISA） method was used to detect serum TNF-α,IL-6,IL-10 levels. Western blot method was used to detect the expression levels of MMP2 and MMP9 proteins in serum. The modified Barthel index（MBI） was used to evaluate the prognosis of spinal tuberculosis patients. Results Compared with control group,serum TNF-α and IL-6 levels and MMP2 and MMP9 expression levels increased（all P〈0. 01）,and serum IL-10 level decreased in spinal tuberculosis group（P〈0. 01）. There were significant differences in serum TNF-α,IL-6,IL-10 levels and MMP2 and MMP9 expression levels in patients with different duration of symptoms（except MMP2 and MMP9 proteins）,different intensity of pain and different erythrocyte sedimentation rate and C-reactive protein level（all P〈0. 01）. Serum TNF-α and IL-6 levels and MMP2 and MMP9 expression levels in good prognosis group of spinal tuberculosis（n = 28） were significantly lower than those in poor prognosis group of spinal tuberculosis（n = 35）（all P〈0. 01）,and serum IL-10 level in good prognosis group of spinal tuberculosis was significantly higher than that in poor prognosis group of spinal tuberculosis（P〈0. 01）.MBI were positively correlated with TNF-α,IL-6 and MMP9 levels（P〈0. 01,P〈0. 05） and negatively correlated with IL-10 level（P〈0. 01） but no significantly correlated with MMP2 level（P〈0. 05）. The receiver operating characteristic curve（ROC） showed that poor prognosis was closely correlated with higher serum TNF-α,IL-6 levels and MMP9 expression level,and good prognosis was closely correlated with serum higher IL-10 level. Conclusions Serum TNF-α,IL-6 levels and MMP2,MMP9 expression levels increase significantly,and serum IL-10 level decreases significantly in patients with spinal tuberculosis,therefore,they are expected to be effective biomarkers for judging the prognosis of spinal tuberculosis.