感染性休克患者血清miR-16-5p和miR-155-5p表达水平及其与预后的关系

doi:10.3760/cma.j.issn.1007-1245.2024.10.006

摘要/Abstract

摘要：

目的　本研究旨在评估感染性休克患者血清miR-16-5p和miR-155-5p表达水平及其与预后的关系。方法　选取2021年6月至2023年7月长安医院急诊科收治的86例确诊为感染性休克的患者（男47例，女39例，<60岁45例，≥60岁41例），根据病情程度分为轻度组30例、中度组29例、重度组27例。对患者进行为期1个月的生存状况统计，基于生存情况将患者划分为死亡组20例和生存组66例。对比各组患者的临床资料，分析miR-16-5p和miR-155-5p表达水平与急性生理学和慢性健康状况评价（APACHEⅡ）评分的相关性，构建受试者操作特征曲线（ROC）分析血清miR-16-5p和miR-155-5p预测感染性休克患者预后的价值，logistic回归分析感染性休克患者预后不良的危险因素。采用独立样本t检验、F检验、χ²检验、Pearson相关性分析。结果　重度组的心率（HR）、C反应蛋白（CRP）、APACHEⅡ评分、miR-16-5p和miR-155-5p表达水平均高于轻度组和中度组（均P<0.05），平均动脉压（MAP）、中心静脉压（CVP）、氧合指数（OI）均低于轻度组和中度组（均P<0.05）。死亡组的CRP、APACHEⅡ评分、miR-16-5p和miR-155-5p表达水平均高于生存组（均P<0.05），OI低于生存组（P<0.05）。Pearson相关性分析显示miR-16-5p和miR-155-5p表达水平与APACHEⅡ评分均呈正相关（r=0.509、0.722，均P<0.001）。血清miR-16-5p联合miR-155-5p预测感染性休克患者预后不良的曲线下面积（AUC）为0.944，95%置信区间（CI）为0.894～0.994，灵敏度为90.0%，特异度为84.8%，显示出较高的预测效能。miR-16-5p和miR-155-5p均为感染性休克患者预后不良的危险因素［OR=10.608（2.275～49.461）、25.410（4.573～141.176），均P<0.05］。结论　在感染性休克患者中，血清miR-16-5p和miR-155-5p表达水平与病情严重程度和预后显著相关，这两种miRNA可作为感染性休克患者预后不良的生物标志物。

关键词:

感染性休克, miR-16-5p, miR-155-5p, 预后, 相关性

Abstract:

Objective　This study aimed to assess the serum levels of miR-16-5p and miR-155-5p in patients with infectious shock, and to explore their relationships with prognosis. Methods　From June 2021 to July 2023, a total of 86 patients diagnosed with infectious shock were selected from the Emergency Department of Chang'an Hospital. There were 47 males and 39 females, 45 cases <60 years old and 41 cases ≥60 years old. These patients were categorized into three groups based on the severity of their condition: mild (30 patients), moderate (29 patients), and severe degree (27 patients). Over a one-month period, the survival status of these patients was monitored, leading to the formation of two groups: a death group (20 patients) and a survival group (66 patients). Comparative analyses of clinical data were conducted across each group. The correlations between the expression levels of miR-16-5p and miR-155-5p and the Acute Physiology and Chronic Health Evaluation (APACHEⅡ) score were analyzed. The receiver operating characteristic curve (ROC) was constructed to assess the prognostic diagnostic values of serum miR-16-5p and miR-155-5p in infectious shock. The risk factors of poor prognosis in patients with infectious shock were analyzed by logistic regression analysis. Independent sample t test, F test, χ² test, and Pearson correlation analysis were used. Results　The heart rate (HR), C-reactive protein (CRP), APACHEⅡ score, and expression levels of miR-16-5p and miR-155-5p in the severe group were higher than those in the mild and moderate groups (all P<0.05), but the mean arterial pressure (MAP), central venous pressure (CVP), and oxygenation index (OI) were lower than those in the mild and moderate groups (all P<0.05). The CRP, APACHEⅡ score, and expression levels of miR-16-5p and miR-155-5p in the death group were higher than those in the survival group (all P<0.05), but the OI was lower than that in the survival group (P<0.05). Pearson correlation analysis showed that the expression levels of miR-16-5p and miR-155-5p were positively correlated with APACHEⅡ score (r=0.509 and 0.722, both P<0.001). The area under the curve (AUC) of serum miR-16-5p combined with miR-155-5p in predicting poor prognosis in patients with infectious shock was 0.944, the 95% confidence interval (CI) was 0.894 - 0.994, the sensitivity was 90.0%, and the specificity was 84.8%, indicating high predictive efficacy. Both miR-16-5p and miR-155-5p were risk factors for poor prognosis in patients with infectious shock [OR=10.608 (2.275-49.461) and 25.410 (4.573-141.176), both P<0.05]. Conclusion　In patients with infectious shock, serum expression levels of miR-16-5p and miR-155-5p are significantly associated with the condition's severity and prognosis. Thus, these two miRNAs may serve as biomarkers for predicting poor prognosis in such patients.

Key words:

Infectious shock, miR-16-5p, miR-155-5p, Prognosis, Correlation

刘刚原平利.

感染性休克患者血清miR-16-5p和miR-155-5p表达水平及其与预后的关系 [J]. 国际医药卫生导报, 2024, 30(10): 1609-1614.

Liu Gang, Yuan Pingli.

Expression levels of serum miR-16-5p and miR-155-5p and their relationships with prognosis in patients with infectious shock [J]. International Medicine and Health Guidance News, 2024, 30(10): 1609-1614.

参考文献

[1] 潘田君,杨玲飞.感染性休克伴急性肾损伤的危险因素及其预后相关因素分析[J].中国现代医学杂志,2017,27(17):98-102. DOI:10.3969/j.issn.1005-8982.2017.17.021.
[2] 王启飞,孙明,张卫平.平均动脉压水平与EICU感染性休克患者肾功能关系的回顾性分析[J].国际医药卫生导报,2023,29(14):1974-1979. DOI:10.3760/cma.j.issn.1007-1245.2023.14.012.
[3] Chandan K, Gupta M, Sarwat M. Role of host and pathogen-derived microRNAs in immune regulation during infectious and inflammatory diseases[J]. Front Immunol, 2020, 10:3081. DOI: 10.3389/fimmu.2019. 03081.
[4] Liu J, Yang T, Huang Z, et al. Transcriptional regulation of nuclear miRNAs in tumorigenesis (Review) [J]. Int J Mol Med, 2022, 50(1):92. DOI: 10.3892/ijmm.2022.5148.
[5] Huang J, Weng Q, Shi Y, et al. MicroRNA-155-5p suppresses PD-L1 expression in lung adenocarcinoma[J]. FEBS Open Bio, 2020, 10(6):1065-1071. DOI: 10.1002/2211-5463.12853.
[6] Lv R, Du L, Zhou F, et al. Rosmarinic acid alleviates inflammation, apoptosis, and oxidative stress through regulating miR-155-5p in a mice model of Parkinson's disease[J]. ACS Chem Neurosci, 2020, 11(20):3259-3266. DOI: 10.1021/acschemneuro.0c00375.
[7] Papagiannopoulos CI, Theodoroula NF, Vizirianakis IS. miR-16-5p promotes erythroid maturation of erythroleukemia cells by regulating ribosome biogenesis[J]. Pharmaceuticals (Basel), 2021, 14(2):137. DOI: 10.3390/ph14020137.
[8] 高戈,冯喆,常志刚,等.2012国际严重脓毒症及脓毒性休克诊疗指南[J].中华危重病急救医学,2013,25(8):501-505. DOI:10.3760/cma.j.issn.2095-4352.2013.08.016.
[9] 张强,ZHAO Liang,许永华,等.急性生理学与慢性健康状况评分系统Ⅱ评分及凝血指标对老年脓毒症患者预后的评估作用[J].中国危重病急救医学,2008,20(8):493-494. DOI:10.3321/j.issn:1003-0603.2008.08.013.
[10] Lopatina T, Widera D, Efimenko A. Editorial: extracellular RNAs as outside regulators of gene expression in homeostasis and pathology[J]. Front Cell Dev Biol, 2022, 9:818430. DOI: 10.3389/fcell.2021.818430.
[11] Dong Q, Han Z, Tian L. Identification of serum exosome-derived circRNA-miRNA-TF-mRNA regulatory network in postmenopausal osteoporosis using bioinformatics analysis and validation in peripheral blood-derived mononuclear cells[J]. Front Endocrinol (Lausanne), 2022, 13:899503. DOI: 10.3389/fendo.2022. 899503.
[12] Zalewski DP, Ruszel KP, Stępniewski A, et al. miRNA regulatory networks associated with peripheral vascular diseases[J]. J Clin Med, 2022, 11(12):3470. DOI: 10.3390/jcm11123470.
[13] Sessa F, Salerno M, Esposito M, et al. miRNA dysregulation in cardiovascular diseases: current opinion and future perspectives[J]. Int J Mol Sci, 2023, 24(6):5192. DOI: 10.3390/ijms24065192.
[14] Ma ZX, Liu Z, Xiong HH, et al. MicroRNAs: protective regulators for neuron growth and development[J]. Neural Regen Res, 2023, 18(4):734-745. DOI: 10.4103/1673- 5374.353481.
[15] O'Connell RM, Kahn D, Gibson WS, et al. MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development[J]. Immunity, 2010, 33(4):607-619. DOI: 10.1016/j.immuni.2010.09.009.
[16] Sonkoly E, Ståhle M, Pivarcsi A. MicroRNAs and immunity: novel players in the regulation of normal immune function and inflammation[J]. Semin Cancer Biol, 2008, 18(2):131-140. DOI: 10.1016/j.semcancer.2008.01.005.
[17] He Y, Cai Y, Pai PM, et al. The causes and consequences of miR-503 dysregulation and its impact on cardiovascular disease and cancer[J]. Front Pharmacol, 2021, 12:629611. DOI: 10.3389/fphar.2021.629611.
[18] Jia X, Wei Y, Miao X, et al. Deficiency of miR-15a/16 upregulates NKG2D in CD8+ T cells to exacerbate dextran sulfate sodium-induced colitis[J]. Biochem Biophys Res Commun, 2021, 554:114-122. DOI: 10.1016/j.bbrc.2021. 03.090.
[19] Trung NT, Lien TT, Sang VV, et al. Circulating miR-147b as a diagnostic marker for patients with bacterial sepsis and septic shock[J]. PLoS One, 2021, 16(12):e0261228. DOI: 10.1371/journal.pone.0261228.
[20] Manetti AC, Maiese A, Paolo MD, et al. MicroRNAs and sepsis-induced cardiac dysfunction: a systematic review[J]. Int J Mol Sci, 2020, 22(1):321. DOI: 10.3390/ijms22010321.
[21] Yao J, Lui KY, Hu X, et al. Circulating microRNAs as novel diagnostic biomarkers and prognostic predictors for septic patients[J]. Infect Genet Evol, 2021, 95:105082. DOI: 10.1016/j.meegid.2021.105082.
[22] Maiese A, Scatena A, Costantino A, et al. Expression of microRNAs in sepsis-related organ dysfunction: a systematic review[J]. Int J Mol Sci, 2022, 23(16):9354. DOI: 10.3390/ijms23169354.
[23] Szilágyi B, Fejes Z, Pócsi M, et al. Role of sepsis modulated circulating microRNAs[J]. EJIFCC, 2019, 30(2):128-145.
[24] Caidengbate S, Akama Y, Banerjee A, et al. MicroRNA profiles in intestinal epithelial cells in a mouse model of sepsis[J]. Cells, 2023, 12(5):726. DOI: 10.3390/cells12050726.
[25] Fouda E, Elrazek Midan DA, Ellaban R, et al. The diagnostic and prognostic role of MiRNA 15b and MiRNA 378a in neonatal sepsis[J]. Biochem Biophys Rep, 2021, 26:100988. DOI: 10.1016/j.bbrep.2021.100988.
[26] Zheng G, Qiu G, Ge M, et al. miR-10a in peripheral blood mononuclear cells is a biomarker for sepsis and has anti-inflammatory function[J]. Mediators Inflamm, 2020, 2020:4370983. DOI: 10.1155/2020/4370983.
[27] Liang G, Wu Y, Guan Y, et al. The correlations between the serum expression of miR-206 and the severity and prognosis of sepsis[J]. Ann Palliat Med, 2020, 9(5):3222-3234. DOI: 10.21037/apm-20-1391.
[28] 刘延霞,麦菁芸,林则彬,等.新生儿脓毒血症血清miR-16-5p、miR-96-5p水平与疾病严重程度和机体炎性反应的相关性研究[J].中国急救复苏与灾害医学杂志,2023,18(9):1185-1188,1210. DOI:10.3969/j.issn.1673- 6966.2023.09.015.
[29] He YX, Huang BL, Yang YY, et al. MicroRNA-16-5p exacerbates sepsis by upregulating aerobic glycolysis via SIRT3-SDHA axis[J]. Cell Biol Int, 2022, 46(12):2207- 2219. DOI: 10.1002/cbin.11908.