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闫祎炜,江 莲,李 梅,张文浩,张文婷,王晓玲,张原苏,张会芬.MMP-9、TIMP-1 水平变化参与 FIRS 早产儿心肌损伤的机制研究[J].中国比较医学杂志,2022,32(6):55~61.
MMP-9、TIMP-1 水平变化参与 FIRS 早产儿心肌损伤的机制研究
Study on the mechanism by which MMP-9 and TIMP-1 levels are involved in myocardial injury in premature infants with FIRS
投稿时间:2021-12-13  
DOI:10. 3969 / j.issn.1671-7856. 2022. 06. 008
中文关键词:  胎儿炎症反应综合征  心肌损伤  金属基质蛋白酶-9  金属蛋白酶组织抑制因子-1  白介素-6
英文关键词:FIRS  myocardial damage  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  
王晓玲 河北医科大学第四医院病理科,石家庄 050000  
张原苏 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  
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中文摘要:
       目的 通过临床研究及构建小鼠胎儿炎症反应综合征( fetal inflammatory response syndrome,FIRS) 模型,探究早产儿 FIRS 体内 MMP-9 / TIMP-1 表达水平变化参与 FIRS 引发心肌损害的可能机制及其潜在药物的发掘。 方法 本研究分为临床观察和动物实验两部分。临床部分:纳入 2018 年 5 月至 2019 年 12 月于河北医科大学第四医院生产的全部早产儿 118 例作为研究对象,根据是否诊断 FIRS 分为 FIRS 组( n= 61)和非 FIRS 组( n= 57) ,比较两组患儿 IL-6、MMP-9、TIMP-1、MMP-9 / TIMP-1(M / T)比值水平及心肌损伤发生情况。 动物部分:构建 FIRS 小鼠模型,根据不同药物干预方式,分为 FIRS 组、RA 组、对照组,留取 3 组小鼠心脏及胎盘组织,观察心脏及胎盘组织病理改变及心脏组织中 IL-6、MMP-9、TIMP-1、MMP-9 / TIMP-1(M / T)比值水平变化。 结果 临床部分:FIRS 组 IL-6、MMP-9、TIMP-1 及 M / T 比值分别为( 38. 53 ± 9. 01) pg / L、 ( 42. 27 ± 12. 53) ng / L、 ( 110. 48 ± 17. 06) ng / L、(38. 30± 9. 93)%,显著高于非 FIRS 组,差异具有统计学意义( P< 0. 05) ; FIRS 组心肌损伤率 (27. 87%)显著高于非 FIRS 组(5. 26%) ,差异具有统计学意义(P= 0. 001) 。动物部分:FIRS 组小鼠心肌组织明显水肿、心室壁变薄,RA 干预后心脏结构变化程度减轻。不同时间点 FIRS 组小鼠 IL-6、MMP-9、TIMP-1 mRNA 表达量及 M / T 比值显著高于对照组(P<0. 05) ;RA 干预后,相同时间节点 IL-6、MMP-9 mRNA 表达量及 M / T 比值显著高于对照组(P<0. 05) ,但是低于 FIRS 组(P<0. 05) 。 结论 FIRS 可通过释放 IL-6,调节 MMP-9、TIMP-1 及 M / T 比值水平,介导早产儿心肌损伤的发生,应用 MMP-9 抑制类药物可在心肌损伤过程中发挥保护作用,为发掘临床潜在治疗药物提供线索。
英文摘要:
       Objective To explore, by constructing a mouse fetal inflammatory response syndrome ( FIRS) model, the possible mechanism by which MMP-9/ TIMP-1 expression in premature infants with FIRS induces myocardial damage and potential drugs against this. Methods This study was divided into two parts: clinical observation and animal experiment. In part 1, a total of 118 premature infants who were in the Fourth Hospital of Hebei Medical University during the period from May 2018 to December 2019 were included as the study participants. According to whether FIRS was diagnosed, they were divided into the FIRS group (n= 61) and control group ( n= 57). The levels of IL-6, MMP-9 and TIMP-1, the MMP-9/ TIMP-1 ( M/ T) ratio, and the occurrence of myocardial injury were compared between the two groups. For part 2 ( the animal experiment), FIRS mice were constructed and divided into the following three drug intervention groups: FIRS group, RA(retinoic acid)group, and control group. Heart tissue was collected from the mice in these groups and used to detect the IL-6, MMP-9 and TIMP-1 levels and the M/ T ratio. Results The IL-6, MMP-9 and TIMP-1 levels and M/ T ratio in the FIRS group were: (38. 53±9. 01) pg / L, (42. 27±12. 53) ng / L, (110. 48±17. 06) ng / L and (38. 30±9. 93)%, respectively; these values were significantly higher (P<0. 05) than those in the non-FIRS group. The myocardial injury rate was significantly higher (P= 0. 001) in the FIRS group (27. 87%) than in the non-FIRS group (5. 26%). In the myocardial tissue of mice in the FIRS group, there were significant levels of edema, the ventricular wall became thinner, and the degree of cardiac structure changes was reduced by RA intervention. The IL-6, MMP-9 and TIMP-1 mRNA expression levels and M/ T ratios in the FIRS group at different timepoints were significantly higher than those in the control group (P<0.05), whereas the the mRNA expression of IL-6 ,MMP-9 levels and M/ T ratios in the RA group were significantly higher than those in the control group (P<0. 05) but were lower than those in the FIRS group (P<0.05). Conclusions FIRS can mediate the occurrence of heart injury in premature infants by releasing IL-6 and by regulating the levels of MMP-9 and TIMP-1 and the M/ T ratio. The application of RA can play a protective role in the process of heart injury and could be a potential drug for providing clinical treatment of FIRS.
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