目的 探究心理应激阳性的官兵血清微小RNA(miRNA)表达谱差异及潜在生物标志物。方法 随机选择某部复杂作业环境的100名青年官兵作为研究对象,通过对其任务前后进行心理测试的方法选出心理应激阳性人员。对参加测试的人员在任务前后分别采血。送检的32个样本(共计16对,8对心理应激阴性样本,8对心理应激阳性样本)利用GeneChip® miRNA 4.0芯片分别检测心理应激阳性人员前后两次血清中miRNA表达差异,以及任务前和任务后血清中miRNA的表达差异。结合miRanda和Targetscan数据库筛选差异miRNA下游靶基因。通过KEGG分析心理应激阳性组中激活的信号通路。选取差异最明显的miRNA,利用RT-qPCR进行验证。结果 基因芯片检测结果共筛查出22个差异显著的miRNA。其中差异最明显的有4个miRNA,其中下调的包含hsa-miR-619-5p、hsa-miR-195-3p、hsa-miR-3196,上调的包含hsa-miR-378h。此外,我们共发现下游差异的靶基因64 019个。KEGG富集分析结果显示心理应激阳性组中转录因子BR相关信号通路显著激活。RT-qPCR检测验证了最明显的差异miRNA,结果与芯片检测结果一致。结论 心理应激阳性官兵血清中miRNA表达存在差异,其中hsa-miR-619-5p、hsa-miR-195-3p、hsa-miR-3196和 hsa-miR-378h特异性和敏感性较高,可能作为官兵心理应激阳性的生物标志物。
Abstract
Objective To investigate the differences in the expression profiles of microRNAs (miRNAs) in the serum of military personnel with positive psychological stress and the potential biomarkers. Methods A total of 100 young military personnel from a complex operational environment were randomly selected as the study subjects. The participants with positive psychological stress were identified using psychological assessments before and after the tasks, and their blood samples were collected accordingly. A total of 32 samples (16 pairs in total, comprising 8 pairs from the psychological stress negative group and 8 pairs from the psychological stress-positive group) were tested using the GeneChip miRNA 4.0 array for the differences in miRNAs expression before and after the tasks. The downstream target genes of the differentially expressed miRNA were screened using miRanda and Targetscan databases. Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to analyze the activated signaling pathways in the positive psychological stress group. The miRNAs with the most obvious differences were selected and verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results A total of 22 miRNAs with significant differences were detected by gene chip detection. There were four miRNAs with the most obvious differences, among which the down-regulated miRNAs were hsa-miR-619-5p, hsa-miR-195-3p and hsa-miR-3196, and the up-regulated miRNAs was hsa-miR-378h. In addition, 64 019 differentially expressed downstream target genes were discovered. KEGG enrichment analysis showed that the transcription factor BR-related signaling pathway was significantly activated in the positive psychological stress group. RT-qPCR results confirmed the most distinct miRNAs, and the results were consistent with the results of chip detection. Conclusions There are differences in the expression of miRNAs in the serum of military personnel with positive psychological stress, among which hsa-miR-619-5p, hsa-miR-195-3p, hsa-miR-3196 and hsa-miR-378h have high specificity and sensitivity, which may be used as biomarkers for positive psychological stress in military personnel.
关键词
应激阳性 /
miRNA /
特异性 /
生物标志物 /
复杂环境
Key words
stress positive /
miRNA /
specificity /
biomarker /
complex environment
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Fleshner M, Crane C R. Exosomes DAMPs and miRNA:features of stress physiology and immune homeostasis[J]. Trends immunol,2017,38(10):768-776.
[2] 陈 叶, 吴雨佳, 周晓斌, 等. 战斗应激反应干预策略的研究进展[J].武警医学, 2026, 31(1):67-71.
[3] Rodgers A B, Morgan C P, Bronson S L, et al. Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation[J].J Neurosci,2013,33(21):9003-9012.
[4] Barwari T, Joshi A, Mayr M. MicroRNAs in cardiovascular disease[J]. J Am Coll Cardiol,2016, 68 (23):2577-2584.
[5] Rupaimoole R, Slack F J. MicroRNA therapeutics:towards a new era for the management of cancer and other diseases[J]. Nat Rev Drug Discov,2017,16(3):203-222.
[6] Nunomura A, Perry G. RNA and oxidative stress in Alzheimer’s disease:focus on microRNAs[J]. Oxid Med Cell Longev, 2020,30:2638130.
[7] Martínez P M, Hidalgo M A, Romero C S, et al. MRNA and miRNA expression patterns associated to pathways linked to metal mixture health effects[J]. Gene,2014,533(2):508-514.
[8] Lucassen P J, Pruessner J, Sousa N, et al. Neuropathology of stress[J].Acta Neuropathol,2014, 127(1):109-135.
[9] Miller M W, Lin A P, Wolf E J, et al. Oxidative stress, inflammation, and neuroprogression in chronic PTSD[J]. Harv Rev Psychiatry,2018,26(2):57-69.
[10] Karam B S, Chavez M A, Koh W, et al. Oxidative stress and inflammation as central mediators of atrial fibrillation in obesity and diabetes[J]. Cardiovasc Diabetol,2017,16(1):120.
[11] 马 南,耑 冰,李 萍,等.氧化应激失衡在支气管哮喘急性发作中的意义[J].中华全科医学,2019, 17(12):1993-1997.
[12] 郭 华,王旭玲.葛根素对糖尿病合并颈动脉硬化患者氧化应激和血液流变学的影响[J].世界中医药, 2018, 13(10):2526-2529.
[13] 陈长兴,仲卫红,金灵璐,等.乌头汤抑制膝骨关节炎软骨细胞氧化应激反应的作用研究[J].风湿病与关节炎,2022,11(11):1-4,15.
[14] 李玲梅,曾德润,张晓红,等.头孢克肟对感染性肠炎小儿对全身炎症应激反应、肠黏膜屏障损伤的影响[J].海南医学院学报,2018,24(8):849-852.
[15] Shi Y, Liu Z, Lin Q, et al. MiRNAs and cancer:key link in diagnosis and therapy[J]. Genes (Basel), 2021,23 (8):1289.
[16] Heris H V, Zahraei Z. MiRNAs:regulators of immune system in diabetes[J].Mutat Res Rev Mutat Res, 2022, 90:108442.
[17] Yang R, Kannan S, Gautam A, et al.Long-Term miRNA changes predicting resiliency factors of post-traumatic stress disorder in a large military cohort-millennium cohort study[J]. Int J Mol Sci,2025, 26(11):45.
[18] Shen L, Zhou T, Wang J, et al. Daphnetin reduces endotoxin lethality in mice and decreases LPS-induced inflammation in Raw264.7 cells via suppressing JAK/STATs activation and ROS production[J]. Inflamm Res, 2017, 66(7):579-589.
[19] Kang T, Zhu J, Luo X, et al. Controlled self-assembly of a close-packed gold octahedra array for SERS sensing exosomal microRNAs[J]. Anal Chem,2021,93(4):2519-2526.
[20] Rauch P J, Gopakumar J, Silver A J, et al. Loss-of-function mutations in dnmt3a and tet2 lead to accelerated atherosclerosis and concordant macrophage phenotypes[J]. Nat Cardiovasc Res, 2023, 2(9):805-818.
[21] Han X, Kan H, Shi J, et al. Isoflurane preconditioning alleviates hypoxia/reoxygenation-induced cardiomyocyte injury by inhibiting mir-195-3p expression[J]. Cardiovasc Toxicol, 2024, 24(7):637-645.
[22] Xiong J, Ma F, Ding N, et al. miR-195-3p alleviates homocysteine-mediated atherosclerosis by targeting IL-31 through its epigenetics modifications[J]. Aging Cell, 2021, 20(10):e13485.
[23] Yao L, Gong X, Liu Y, et al. The miR-195-3p/BDNF axis is a promising therapeutic for heart failure[J]. Int J Cardiol, 2024, 406:131991.
[24] Miller K E, Mac J P, Sullivan L, et al. Salivary miRNA expression in children with persistent post-concussive symptoms[J]. Front Public Health, 2022, 10:890420.
[25] Escate R, Padró T, Suades R, et al. miR-619-5p and cardiogenic shock in patients with ST-segment elevation myocardial infarction[J]. Eur J Clin Invest, 2024, 54(8):e14186.
[26] Pan H Q, Liu W Z, Yang C Z,et al. Enhanced rap1 small GTPase activity in the ventral hippocampus drives stress-induced anxiety[J]. Sci Adv, 2025, 11(21):eadt3163.
[27] Zhao Y, Chen Y, Guo C, et al. Chronic stress dysregulates the Hippo/YAP/14-3-3η pathway and induces mitochondrial damage in basolateral amygdala in a mouse model of depression[J]. Theranostics, 2024, 14(9):3653-3673.
[28] Zhao Z, Liu P, Zhang H, et al. Gastrodin prevents stress-induced synaptic plasticity impairment and behavioral dysfunction via cAMP/PKA/CREB signaling pathway[J]. Phytomedicine, 2025, 141:156661.
PDF(4737 KB)
