外科理论与实践

外科理论与实践 ›› 2020, Vol. 25 ›› Issue (04): 315-321.doi: 10.16139/j.1007-9610.2020.04.010

• 论著 • 上一篇    下一篇

创伤病人血清游离线粒体含量变化及其临床意义

郭恩伟, 任大力, 章冰玉, 杨峰, 姚峪岚, 贾凌, 余琳, 冯刚()   

  1. 海军军医大学附属公利医院重症医学科,上海 200135
  • 收稿日期:2020-01-07 出版日期:2020-07-25 发布日期:2022-07-18
  • 通讯作者: 冯刚 E-mail:92102fg@sina.com
  • 基金资助:
    上海市浦东新区卫生和计划生育委员会科技项目(PW2014A-31);上海市浦东新区卫生和计划生育委员会重点专病建设项目(PWZzb2017-18)

Change in amount of serum cell-free mitochondrial DNA and clinical relevance in trauma patients

GUO Enwei, REN Dali, ZHANG Bingyu, YANG feng, YAO Yulan, JIA Ling, YU Lin, FENG Gang()   

  1. Department of Critical Care Medicine, Gongli Hospital Affiliated to Naval Medical University, Shanghai 200135, China
  • Received:2020-01-07 Online:2020-07-25 Published:2022-07-18
  • Contact: FENG Gang E-mail:92102fg@sina.com

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摘要：

目的：研究创伤病人血清游离线粒体DNA（cell-free mitochondrial DNA, cf-mtDNA）含量变化及其与炎症反应的关系,探讨其临床价值。方法：创伤病人37例为创伤组,根据损伤程度分为多发伤组和单发伤组,及休克组和无休克组。10名健康志愿者为对照组。分别比较创伤组和对照组及创伤各亚组创伤后4 h、24 h、72 h和7 d时间点血清cf-mtDNA、 C反应蛋白（C-reactive protein, CRP）、 肿瘤坏死因子α（tumor necrosis factor-α,TNF-α）、白细胞介素6（interleukin-6,IL-6）含量差异,分析血清cf-mtDNA含量与损伤严重程度评分（injury severity score, ISS）、全身炎症反应综合征（systemic inflammatory response syndrome, SIRS）评分和血清CRP、TNF-α、IL-6含量的相关性。应用受试者工作特征（receiver operating characteristic, ROC）曲线评估创伤后血清cf-mtDNA含量诊断炎症反应的价值。结果：创伤病人伤后24 h、72 h血清cf-mtDNA含量明显高于对照组（均P<0.05）。多发伤组病人伤后4 h、24 h、72 h、7 d血清cf-mtDNA含量均明显高于单发伤组（分别P<0.05,P<0.01,P<0.01,P<0.05）。休克组病人伤后24 h血清cf-mtDNA含量明显高于无休克组病人（P<0.01）。创伤并发器官功能损伤组病人伤后4 h、24 h血清cf-mtDNA相对含量明显高于无并发器官功能损伤组（均P<0.05）。死亡病人血清cf-mtDNA含量峰值虽高于生存组,但差异无统计学意义（P>0.05）。随着创伤后血清cf-mtDNA含量升高的同时,血清TNF-α、IL-6、CRP含量也显著升高。创伤后24 h血清cf-mtDNA含量与ISS成正相关（r=0.454,P=0.004）。创伤后4 h~7 d血清cf-mtDNA含量分别与 SIRS评分、血清IL-6含量成正相关（分别r=0.458,P=0.000 1;r=0.252,P=0.005）,但与血清TNF-α含量不相关（r=-0.058,P=0.511）。创伤后4~24 h血清cf-mtDNA含量与血清CRP含量成正相关（r=0.264,P=0.028）。创伤后4 h~7 d血清cf-mtDNA含量诊断炎症反应ROC曲线下面积为0.752（P=0.000 01）,95%CI：0.668~0.836。根据最大约登指数计算结果,最佳临界值为0.075 3,其诊断炎症反应的灵敏度为63.6%,特异度为85.5%。结论：创伤病人创伤后早期血清cf-mtDNA含量升高,高血清cf-mtDNA含量表明创伤和炎症反应程度重。创伤后早期血清cf-mtDNA含量对炎症反应的诊断具有一定价值。

关键词: 创伤, 游离线粒体DNA, C反应蛋白, 全身炎症反应综合征, 细胞因子

Abstract:

Objective To investigate change in amount of serum cell-free mitochondrial DNA (cf-mtDNA) related with inflammatory response and to explore clinical relevance to trauma patients. Methods Thirty-seven trauma patients as trauma group were divided as multiple trauma subgroup or single trauma subgroup, and as shock subgroup or non-shock subgroup. Ten healthy volunteers were as control group. The amount of cf-mtDNA in serum at 4 h, 24 h, 72 h, 7 d post-injury was compared between trauma group and control group and among subgroups. The association of serum cf-mtDNA with injury severity score (ISS), systemic inflammatory response syndrome (SIRS) score, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were analyzed respectively. The receiver operating characteristic (ROC) curve of serum cf-mtDNA post-injury were constructed to evaluate role in diagnosing SIRS. Results Serum cf-mtDNA in trauma patients at 24 h, 72 h post-injury were significantly higher than those in control group (P<0.05). Serum cf-mtDNA of patients in multiple trauma subgroup were significantly higher than those in single trauma subgroup at 4 h, 24 h, 72 h, 7 d post-injury (P<0.05, P<0.01, P<0.01, P<0.05). The amount of serum cf-mtDNA in shock subgroup were significantly higher than that in non-shock subgroup at 24 h post-injury (P<0.01), and that in group of organ dysfunction higher than in group without organ dysfunction at 4 h, 24 h post-injury (P<0.05). The peak of serum cf-mtDNA in dead patients was hi-gher than survived patients without statistical significance (P>0.05). Amounts of TNF-α, IL-6 and CRP in serum increased with serum cf-mtDNA post-injury. Amount of serum cf-mtDNA correlated positively with ISS at 24 h post-injury (r=0.454, P=0.004), with SIRS score and serum IL-6 at 4 h-7 d post-injury respectively(r=0.458, P=0.000 1; r=0.252, P=0.005), but did not correlate with serum TNF-α (r=-0.058, P=0.511), and with CRP at 4-24 h post-injury positively (r=0.264, P=0.028). The area under ROC curve of serum cf-mtDNA was 0.752 at 4 h-7 d post-injury (P=0.000 01), with 95% confidence interval of 0.668-0.836. According to maximum Youden index, the optimal cutoff value of serum cf-mtDNA was 0.075 2 with the sensitivity 63.6% and specificity 85.5% for diagnosis of SIRS. Conclusions The amount of serum cf-mtDNA increased in trauma patients at early stage, indicating severe trauma and inflammation, and more amount of serum cf-mtDNA would be helpful to diagnose SIRS.

Key words: Trauma, Cell-free mitochondrial DNA, C-reactive protein, Systemic inflammatory response syndrome, Cytokine

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