创伤病人血清游离线粒体含量变化及其临床意义
收稿日期: 2020-01-07
网络出版日期: 2022-07-18
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
Received date: 2020-01-07
Online published: 2022-07-18
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。
郭恩伟, 任大力, 章冰玉, 杨峰, 姚峪岚, 贾凌, 余琳, 冯刚 . 创伤病人血清游离线粒体含量变化及其临床意义[J]. 外科理论与实践, 2020 , 25(04) : 315 -321 . DOI: 10.16139/j.1007-9610.2020.04.010
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.
| [1] | Soreide K. Epidemiology of major trauma[J]. Br J Surg, 2009, 96(7):697-698. |
| [2] | Zhang Q, Raoof M, Chen Y, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury[J]. Nature, 2010, 464(7285):104-107. |
| [3] | Lam NY, Rainer TH, Chiu RW, et al. Plasma mitochondrial DNA concentrations after trauma[J]. Clin Chem, 2004, 50(1):213-216. |
| [4] | Thurairajah K, Briggs GD, Balogh ZJ. The source of cell-free mitochondrial DNA in trauma and potential therapeutic strategies[J]. Eur J Trauma Emerg Surg, 2018, 44(3):325-334. |
| [5] | McIlroy DJ, Bigland M, White AE, et al. Cell necrosis-independent sustained mitochondrial and nuclear DNA release following trauma surgery[J]. J Trauma Acute Care Surg, 2015, 78(2):282-288. |
| [6] | Yamanouchi S, Kudo D, Yamada M, et al. Plasma mitochondrial DNA levels in patients with trauma and severe sepsis: Time course and the association with clinical status[J]. J Crit Care, 2013, 28(6):1027-1031. |
| [7] | Hu Q, Zhou Q, Wu J, et al. The role of mitochondrial DNA in the development of ischemia reperfusion injury[J]. Shock, 2019, 51(1):52-59. |
| [8] | Gu X, Yao Y, Wu G, et al. The plasma mitochondrial DNA is an independent predictor for post-traumatic systemic inflammatory response syndrome[J]. PLoS One, 2013, 8(8):e72834. |
| [9] | Wang HC, Lin YJ, Tsai NW, et al. Serial plasma deo-xyribonucleic acid levels as predictors of outcome in acute traumatic brain injury[J]. J Neurotrauma, 2014, 31(11):1039-1045. |
| [10] | Zhang J, Chen X, Liu Z, et al. Association between plasma mitochondrial DNA and sterile systemic inflammatory response syndrome in patients with acute blunt traumatic injury[J]. Int J Clin Exp Med, 2017, 10:3254-3262. |
| [11] | Gu X, Wu G, Yao Y, et al. Intratracheal administration of mitochondrial DNA directly provokes lung inflammation through the TLR9-p38 MAPK pathway[J]. Free Radic Biol Med, 2015, 83:149-158. |
| [12] | Xie L, Liu S, Cheng J, et al. Exogenous administration of mitochondrial DNA promotes ischemia reperfusion injury via TLR9-p38 MAPK pathway[J]. Regul Toxicol Pharmacol, 2017, 89:148-154. |
| [13] | West AP, Koblansky AA, Ghosh S. Recognition and signaling by toll-like receptors[J]. Annu Rev Cell Dev Biol, 2006, 22:409-437. |
| [14] | Zhang Q, Itagaki K, Hauser CJ. Mitochondrial DNA is released by shock and activates neutrophils via P38 map kinase[J]. Shock, 2010, 34(1):55-59. |
| [15] | Zhang JZ, Liu Z, Liu J, et al. Mitochondrial DNA induces inflammation and increases TLR9/NF-κB expression in lung tissue[J]. Int J Mol Med, 2014, 33(4):817-824. |
| [16] | Timmermans K, Kox M, Scheffer GJ, et al. Plasma nuc-lear and mitochondrial DNA levels, and markers of inflammation, shock, and organ damage in patients with septic shock[J]. Shock, 2016, 45(6):607-612. |
| [17] | Qin C, Gu J, Liu R, et al. Release of mitochondrial DNA correlates with peak inflammatory cytokines in patients with acute myocardial infarction[J]. Anatol J Cardiol, 2017, 17(3):224-228. |
| [18] | Simmons JD, Lee YL, Mulekar S, et al. Elevated levels of plasma mitochondrial DNA DAMPs are linked to clinical outcome in severely injured human subjects[J]. Ann Surg, 2013, 258(4):591-598. |
| [19] | Aswani A, Manson J, Itagaki K, et al. Scavenging circulating mitochondrial DNA as a potential therapeutic option for multiple organ dysfunction in trauma hemorrhage[J]. Front Immunol, 2018, 9:891. |
| [20] | Faust HE, Reilly JP, Anderson BJ, et al. Plasma mitochondrial DNA levels are associated with ARDS in trauma and sepsis patients[J]. Chest, 2020, 157(1):67-76. |
| [21] | McIlroy DJ, Minahan K, Keely S, et al. Reduced deo-xyribonuclease enzyme activity in response to high postinjury mitochondrial DNA concentration provides a therapeutic target for systemic inflammatory response syndrome[J]. J Trauma Acute Care Surg, 2018, 85(2):354-358. |
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