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闫祎炜,江 莲,李 梅,张会芬,沈 颖,张文浩,张文婷.FIRS 早产儿脐血 MMP-9、TIMP-1 水平变化及其与肺损伤关系的研究[J].中国比较医学杂志,2021,31(11):35~41.
FIRS 早产儿脐血 MMP-9、TIMP-1 水平变化及其与肺损伤关系的研究
Influence of FIRS on matrix metalloprotein-9 or tissue inhibitor of metalloproteinases 1 levels in cord blood of premature infants and its relationship with lung injury
投稿时间:2021-03-03  
DOI:10. 3969 / j.issn.1671-7856. 2021. 11. 006
中文关键词:  胎儿炎症反应综合征  支气管肺炎发育不良  MMP-9  TIMP-1  IL-6
英文关键词:FIRS  bronchopneumonia dysplasia  MMP-9  TIMP-1  IL-6
基金项目:
作者单位E-mail
闫祎炜 河北医科大学第四医院儿科,石家庄 050000 yanyiwei2012@ 126.com 
江 莲 河北医科大学第四医院儿科,石家庄 050000 jianglianerke@ 163.com 
李 梅 河北医科大学第四医院儿科,石家庄 050000  
张会芬 河北医科大学第四医院儿科,石家庄 050000  
沈 颖 河北医科大学第四医院儿科,石家庄 050000  
张文浩 河北医科大学第四医院儿科,石家庄 050000  
张文婷 河北医科大学第四医院儿科,石家庄 050000  
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中文摘要:
       目的 探究 FIRS 早产儿 MMP-9、TIMP-1 表达紊乱与支气管肺发育不良的关系和初步机制。 方法 本研究设计临床和动物实验两部分。临床部分:纳入 2018 年 5 月~2019 年 12 月早产儿 118 例,分为对照组及研究组,留取各组患儿出生后脐血及产妇胎盘组织。 以观察炎症指标 IL-6、MMP-9、TIMP-1、MMP-9/ TIMP-1(M/ T)比值及病理组织炎症浸润情况,并分析炎症指标之间的关系。动物实验:制备孕鼠,分别通过不同干预方式,将胎鼠及新生鼠分为 3 组,FIRS 组(LPS 脂多糖干预)、RA 组(维甲酸干预)、NS 组(生理盐水干预),均留取肺组织。观察小鼠肺组织炎症指标及胎盘病理组织炎症浸润情况。 结果 临床部分:不同胎龄 FIRS 组早产儿脐血中 IL-6、MMP- 9、TIMP-1 及 M/ T 比值表达水平较对照组显著增加(P<0. 01);FIRS 组 BPD 发生率高于同胎龄对照组。动物实验部分:不同日龄 FIRS 组胎鼠 IL-6、MMP-9、TIMP-1 及 M/ T 比值均明显高于同日龄对照组(P<0. 01)。 RA 干预后: 同时期炎症指标高于同日龄对照组(P<0. 01),但低于同日龄 FIRS 组(P<0. 01)。 结论 FIRS 可能通过调节 MMP- 9、TIMP-1 水平及 M/ T 比值,介导 BPD 发生,应用 MMP-9 抑制剂可在肺损伤过程中发挥保护作用,为临床治疗提供了潜在的药物治疗靶点。
英文摘要:
       Objective To explore the relationship between expression of matrix metalloprotein-9 (MMP-9) and tissue inhibitor of metalloproteinases 1 ( TIMP-1) in premature infants with FIRS and bronchopulmonary dysplasia. Methods This study was designed with clinical and animal experiments. Clinical experiments: From May 2018 to December 2019, 118 preterm samples were obtained and divided into control group and experimental group, to observe inflammatory indicators (IL-6, MMP-9, TIMP-1 and M/ T ratio) and pathological tissue infiltration by inflammatory cells and analyze the relationship between inflammatory indicators of the groups. Animal experiments: Establish the pregnant mice and randomly divided them into three groups, lipopolysaccharide group (LPS, n= 10), retinoic acid group (RA, n= 10) and normal saline group (NS, n= 10). The inflammatory indexes of lung tissues and inflammatory cell infiltration in placental pathological tissues in the three groups were assessed, and the relationship between the inflammatory indexes of the three groups was analyzed. Results The expression levels of IL-6, MMP-9, TIMP-1 and the M/ T ratio in cord blood of premature infants in the FIRS group of different gestational ages were significantly higher than those in the control group (P<0. 01). The incidence of BPD in the FIRS group was higher than that in the control group at the same gestational age. Animal experiments: The expression levels of MMP-9 and TIMP-1 and the M/ T ratio in newborn (fetal) rats of different FIRS age groups were significantly higher than those of the control group at the same age (P<0. 01). After RA treatment, the inflammatory index was higher than that in the control group at the same age (P<0. 01), but lower than that in the FIRS group at the same age (P<0. 01). IL-6 was positively correlated with MMP-9, TIMP-1 and the M/ T ratio in mice lung tissue. Conclusions FIRS regulates MMP-9, TIMP-1 levels and the M/ T ratio, mediates BPD and the application of an MMP-9 inhibitor plays a protective role in the process of lung injury, which provides a potential drug target for clinical treatment.
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