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中国防痨杂志 ›› 2022, Vol. 44 ›› Issue (2): 164-168.doi: 10.19982/j.issn.1000-6621.20210627

• 论著 • 上一篇    下一篇


陆霓虹1, 沈凌筠2, 刘洪璐1, 陈杨君1, 杜映荣3()   

  1. 1昆明市第三人民医院呼吸与危重症医学科,昆明 650041
    2昆明市第三人民医院结核科,昆明 650041
    3昆明市第三人民医院传染病临床研究中心,昆明 650041
  • 收稿日期:2021-10-22 出版日期:2022-02-10 发布日期:2022-02-14
  • 通信作者: 杜映荣
  • 基金资助:

Analysis of correlation between the level of matrix metalloproteinases and anti-tuberculosis drug-induced liver injury

LU Ni-hong1, SHEN Ling-jun2, LIU Hong-lu1, CHEN Yang-jun1, DU Ying-rong3()   

  1. 1Department of Respiratory and Critical Care Medicine, the Third People’s Hospital of Kunming, Kunming 650041, China
    2Department of Tuberculosis, the Third People’s Hospital of Kunming, Kunming 650041, China
    3Infectious Disease Clinical Research Center, the Third People’s Hospital of Kunming, Kunming 650041, China
  • Received:2021-10-22 Online:2022-02-10 Published:2022-02-14
  • Contact: DU Ying-rong
  • Supported by:
    National Natural Science Foundation of China Regional Science Foundation(81960096);Key project of Kunming Science and Technology Plan Project(2019-1-N-25318000003253);Yunnan Provincial Department of Science and Technology Science and Technology Program Project of Local Universities Joint Special Project(202001BA070001-134)


目的: 分析抗结核药物导致的肝损伤(anti-tuberculosis drug-induced liver injury,ATB-DILI)患者基质金属蛋白酶类(matrix metalloproteinases,MMP)水平及其相关性。方法: 采用回顾性研究方法,收集2019年6月至2020年6月昆明市第三人民医院收治的肺结核患者中发生ATB-DILI的98例患者作为病例组;选取同期门诊健康体检者30名作为对照组。采集研究对象晨起空腹静脉血6ml,采用双抗体夹心法检测其MMP-1、MMP-2、MMP-7、MMP-9、MMP-13、MMP-14浓度。病例组研究对象根据ATB-DILI临床分型分为肝细胞损伤型(A组)、胆汁淤积型(B组)、肝血管损伤型(C组)、混合型(D组);根据ATB-DILI严重程度分为0级(无肝损伤)、1级(轻度肝损伤)、2级(中度肝损伤)、3级(重度肝损伤)、4级(急性肝功能衰竭)、5级(致命)。 比较不同临床分型组及对照组研究对象MMP水平;分析MMP水平与ATB-DILI严重程度分级相关性。结果: 按照ATB-DILI临床分型,病例组中A组有51例,B组有12例,C组有15例,D组有20例;根据ATB-DILI严重程度分级,病例组中1级有33例,2级有27例,3级有22例,4级有14例,5级有2例。A、B、C、D组及对照组MMP-1浓度分别为:(89.1±11.2)ng/ml、(32.3±6.3)ng/ml、(47.5±9.1)ng/ml、(55.2±11.1)ng/ml、(27.5±8.2)ng/ml;MMP-2浓度分别为:(8.2±2.1)ng/ml、(6.2±2.3)ng/ml、(15.5±1.8)ng/ml、(7.2±1.6)ng/ml、(3.2±1.3)ng/ml;MMP-9浓度分别为:36.1(25.9,47.3)ng/ml、11.3(5.1,20.6)ng/ml、14.1(6.1,21.3)ng/ml、15.3(3.8,28.1)ng/ml、6.4(2.8,8.6)ng/ml;MMP-14浓度分别为:5.2(2.8,7.5)ng/ml、6.0(3.6,8.9)ng/ml、11.2(5.2,17.4)ng/ml、4.0(1.8,6.2)ng/ml、2.8(1.4,4.3)ng/ml。A组MMP-1和MMP-9浓度明显升高,C组MMP-2和MMP-14浓度明显升高,差异均有统计学意义(F=7.983,P=0.031;H=9.979,P=0.041;F=9.381,P=0.010;H=10.555,P=0.032)。ATB-DILI严重程度1、2、3、4、5级患者MMP-9浓度分别为:16.2(13.2,19.3)ng/ml、21.5(18.4,23.6)ng/ml、24.3(20.6,27.1)ng/ml、30.3(25.1,35.3)ng/ml、38.5(33.9,43.1)ng/ml,与严重程度分级呈正相关(r=0.882, P=0.000)。结论: 不同临床分型ATB-DILI患者MMP-1、MMP-2、MMP-9、MMP-14浓度有不同程度升高;MMP-9浓度与ATB-DILI严重程度呈正相关;MMP水平可能为ATB-DILI发生的影响因素。

关键词: 基质金属蛋白酶类, 药物性肝损伤, 抗结核药, 回归分析


Objective: To analyze levels of matrix metalloproteinases (MMP) and the correlation between the levels and anti-tuberculosis drug-induced liver injury (ATB-DILI). Methods: A retrospective research was conducted in 98 pulmonary tuberculosis patients with ATB-DILI treated in the Third People’s Hospital of Kunming from June 2019 to June 2020 (case group), and 30 outpatients with physical examination in the same period were selected as the control group. A total of 6 ml fasting venous blood was collected from the subjects in the morning. The concentrations of MMP-1, MMP-2, MMP-7, MMP-9, MMP-13 and MMP-14 were detected by double antibody sandwich method. According to the clinical classification of ATB-DILI, the subjects of the case group were divided into hepatocyte injury type (group A), cholestasis type (group B), hepatic vascular injury type (group C), and mixed type (group D); according to the severity of ATB-DILI, they were divided into grade 0 (no liver injury), grade 1 (mild liver injury), grade 2 (moderate liver injury), grade 3 (severe liver injury), grade 4 (acute liver failure), and grade 5 (lethal). The MMP levels of different clinical classification groups and the control group were compared, and the correlation between MMP levels and ATB-DILI severity classification was analyzed. Results: According to ATB-DILI clinical classification, there were 51 cases in group A, 12 cases in group B, 15 cases in group C, and 20 cases in group D. According to the ATB-DILI severity classification, there were 33 cases in grade 1, 27 cases in grade 2, 22 cases in grade 3, 14 cases in grade 4, and 2 cases in grade 5. In groups A, B, C, D and control group, concentrations of MMP-1 were (89.1±11.2) ng/ml, (32.3±6.3) ng/ml, (47.5±9.1) ng/ml, (55.2±11.1) ng/ml, and (27.5±8.2) ng/ml, respectively; MMP-2 concentrations were (8.21±2.1) ng/ml, (6.2±2.3) ng/ml, (15.5±1.8) ng/ml, (7.2±1.6) ng/ml, and (3.2±1.3) ng/ml, respectively; MMP-9 concentrations were 36.1 (25.9, 47.3) ng/ml, 11.3 (5.1, 20.6) ng/ml, 14.1 (6.1, 21.3) ng/ml, 15.3 (3.8, 28.1) ng/ml, and 6.4 (2.8, 8.6) ng/ml, respectively; MMP-14 concentrations were 5.2 (2.8, 7.5) ng/ml, 6.0 (3.6, 8.9) ng/ml, 11.2 (5.2, 17.4) ng/ml, 4.0 (1.8, 6.2) ng/ml, 2.8 (1.4, 4.3) ng/ml. The concentrations of MMP-1 and MMP-9 in group A were significantly increased, and the concentrations of MMP-2 and MMP-14 in group C were also significantly increased, both the differences were statistically significant (F=7.983, P=0.031; H=9.979, P=0.041; F=9.381, P=0.010; H=10.555, P=0.032). MMP-9 concentrations in patients with ATB-DILI severity 1, 2, 3, 4, and 5 were 16.2(13.2, 19.3) ng/ml, 21.5(18.4, 23.6) ng/ml, 24.3(20.6, 27.1) ng/ml, 30.3(25.1, 35.3) ng/ml, 38.5(33.9, 43.1) ng/ml respectively, which was positively correlated with the severity classification (r=0.882, P=0.000). Conclusion: The concentrations of MMP-1, MMP-2, MMP-9 and MMP-14 in patients with different clinical types of ATB-DILI increased to different degrees. MMP-9 concentrations are positively correlated with ATB-DILI severity. MMP level may be an influencing factor for the occurrence of ATB-DILI.

Key words: Matrix metalloproteinases, Drug-induced liver injury, Antitubercular agents, Regression analysis