2024 年第 2 期 第 19 卷

脑脊液基质金属蛋白酶9水平和基质金属蛋白酶9/基质金属蛋白酶组织抑制剂1比值与结核性脑膜炎病情严重程度的相关性及对预后的预测价值研究

Study on the correlation of matrix metalloproteinase 9, matrix metalloproteinase 9/tissue inhibitor of metalloproteinases 1 levels with the severity of tuberculous meningitis and their prognostic predictive value

作者：王起1袁甜1方喆1陈红梅2

英文作者：Wang Qi1 Yuan Tian1 Fang Zhe1 Chen Hongmei2

单位：1湖南省胸科医院内一科，长沙410006；2湖南省胸科医院呼吸内科，长沙410006 通信作者：陈红梅,Email:453730409@qq.com

英文单位：1The First Department of Internal Hunan Chest Hospital Changsha 410006 China; 2Department of Respiratory Medicine Hunan Chest Hospital Changsha 410006 China

关键词：结核性脑膜炎；基质金属蛋白酶9；基质金属蛋白酶组织抑制剂1；病情严重程度；预后预测

英文关键词：Tuberculousmeningitis;Matrixmetalloproteinase9;Tissueinhibitorofmetalloproteinases1; Severityofcondition;Prognosticprediction

• 摘要：

• 目的  探讨脑脊液基质金属蛋白酶9（MMP-9）水平和MMP-9/基质金属蛋白酶组织抑制剂1（TIMP-1）比值与结核性脑膜炎病情严重程度的相关性及对预后的预测价值。方法  选择2021年1月至2023年2月在湖南省胸科医院住院的结核性脑膜炎患者72例为观察组，以同期住院的非肿瘤非感染性头痛患者52例为对照组。比较2组患者脑脊液MMP-9水平和MMP-9/TIMP-1比值。根据改良的英国医学研究理事会结核性脑膜炎分期标准将观察组患者分为Ⅰ期组、Ⅱ期组、Ⅲ期组，比较3组患者MMP-9水平和MMP-9/TIMP-1比值。根据预后情况将观察组患者分为预后良好组和预后不良组，比较2组MMP-9水平和MMP-9/TIMP-1比值，并以受试者工作特征（ROC）曲线法评估各指标对结核性脑膜炎的预后预测价值。结果  观察组MMP-9水平及MMP-9/TIMP-1比值均大于对照组［（96±21）μg/L比（50±12）μg/L、（1.21±0.33）比（0.67±0.15）］（均P＜0.05），但2组间TIMP-1水平比较差异无统计学意义（P＞0.05）。不同严重程度结核性脑膜炎患者MMP-9水平及MMP-9/TIMP-1比值差异均有统计学意义，且均呈Ⅰ期＜Ⅱ期＜Ⅲ期（均P＜0.05）；不同严重程度结核性脑膜炎患者TIMP-1水平差异均无统计学意义（均P＞0.05）。相关性分析结果显示，结核性脑膜炎病情严重程度与MMP-9水平及MMP-9/TIMP-1比值均呈正相关（r=0.861、P=0.012；r=0.731、P=0.008），与TIMP-1无相关性（r=0.220，P=0.063）。预后不良组患者MMP-9水平及MMP-9/TIMP-1比值均高于预后良好组（均P＜0.05），2组TIMP-1水平差异无统计学意义（P＞0.05）。ROC曲线分析结果显示，MMP-9水平、MMP-9/TIMP-1比值预测结核性脑膜炎患者预后不良的截断值分别为112.04 μg/L、1.41，曲线下面积分别为0.803、0.905(均P＜0.05)。结论  结核性脑膜炎患者脑脊液MMP-9水平、MMP-9/TIMP-1比值明显升高，且MMP-9水平、MMP-9/TIMP-1比值与结核性脑膜炎的病情严重程度呈正相关，并可用于预测患者预后。

• Objective  To explore the correlation of levels of matrix metalloproteinase 9 (MMP-9), MMP-9/tissue inhibitor of metalloproteinases 1 (TIMP-1) with the severity of tuberculous meningitis, as well as the predictive value of prognosis. Methods  Totally 72 patients with tuberculous meningitis admitted to Hunan Chest Hospital from January 2021 to February 2023 were selected as the observation group, and 52 patients with non tumor and non infectious headache hospitalized at the same time were selected as the control group. According to the improved Medical Research Council staging criteria for tuberculous meningitis, patients in observation group were divided into Phase Ⅰ, Ⅱ, and Ⅲ groups, and the levels of MMP-9 and MMP-9/TIMP-1 in each group were compared. According to the prognosis, patients of observation group were divided into good prognosis group and poor prognosis group, and the levels of MMP-9 and MMP-9/TIMP-1 were compared between the two groups. The receiver operating characteristic (ROC) curve method was used to evaluate the prognostic evaluation efficacy of each indicator for tuberculous meningitis. Results  The levels of MMP-9 and MMP-9/TIMP-1 in the observation group were higher than those in the control group［(96±21)μg/L vs (50±12)μg/L, (1.21±0.33) vs (0.67±0.15)］(both P＜0.05), but there was no statistically significant difference in TIMP-1 between the two groups (P＞0.05). The levels of MMP-9 and MMP-9/TIMP-1 in patients with tuberculous meningitis of different severity levels showed statistically significant differences, and both showed a trend of stage Ⅰ＜stage Ⅱ＜stage Ⅲ (all P＜0.05). There was no statistically significant difference in TIMP-1 levels among patients with tuberculosis meningitis of different severity levels (P＞0.05). The correlation analysis results showed a positive correlation between the severity of tuberculous meningitis and MMP-9 and MMP-9/TIMP-1 (r=0.861, P=0.012； r=0.731, P=0.008). The severity of tuberculous meningitis was not significantly correlated with TIMP-1 (r=0.220, P=0.063). The levels of MMP-9 and MMP-9/TIMP-1 in poor prognosis group were higher than those in good prognosis group (both P＜0.05), and there was no statistically significant difference in TIMP-1 levels between the two groups (P＞0.05). The ROC analysis showed that the cutoff values of MMP-9 and MMP-9/TIMP-1 for predicting poor prognosis in patients with tuberculous meningitis were 112.04 μg/L and 1.41, and the area under the curve was 0.803 and 0.905, respectively (both P＜0.05). Conclusions    The levels of MMP-9 and MMP-9/TIMP-1 in cerebrospinal fluid of patients with tuberculous meningitis were significantly increased, and the levels of MMP-9 and MMP-9/TIMP-1 were positively correlated with the severity of tuberculous meningitis, which can be used to predict patient prognosis.