支气管哮喘患儿外周血miR-9-5p、SOCS5表达水平及与Th1/Th2平衡的关系

doi:10.3760/cma.j.cn441417-20240517-13015

摘要/Abstract

摘要：

目的　探讨支气管哮喘患儿外周血miR-9-5p、SOCS5表达水平及与Th1/Th2平衡的关系。方法　选取2021年6月至2023年6月铜川市妇幼保健院收治的99例支气管哮喘患儿作为研究对象。根据喘息控制情况，将患儿分为发作组（42例）和缓解组（57例）。同期在儿科病房选取4周内没有肺病史、喘息、过敏、呼吸道感染且年龄匹配的患儿作为对照组（52例）。发作组男22例，女20例；年龄（8.30±1.42）岁。缓解组男30例，女27例；年龄（8.57±1.21）岁。对照组男32例，女20例；年龄（8.23±1.36）岁。比较3组miR-9-5p、SOCS5表达水平，辅助性T细胞（Th）1、Th2水平及Th1/Th2，C-反应蛋白（CRP）、白细胞计数（WBC）、免疫球蛋白E（IgE）水平，肺功能指标［第1秒用力呼气容积占预计值百分比（FEV1%）、第1秒用力呼气容积（FEV1）/用力肺活量（FVC）、一氧化碳弥散量（DLCO）］。采用方差分析、SNK-q检验和χ²检验进行统计学分析；采用Pearson相关性分析miR-9-5p、SOCS5表达水平与各指标的关系；采用多因素logistic回归分析患儿哮喘控制水平不良的影响因素。结果　缓解组、发作组miR-9-5p、SOCS5表达水平均高于对照组（均P<0.05）；发作组miR-9-5p、SOCS5表达水平均高于缓解组（均P<0.05）。缓解组、发作组Th1水平及Th1/Th2均低于对照组，Th2水平均高于对照组（均P<0.05）；发作组Th1水平及Th1/Th2均低于缓解组，Th2水平高于缓解组（均P<0.05）。缓解组、发作组CRP、WBC、IgE水平均高于对照组（均P<0.05）；发作组CRP、WBC、IgE水平均高于缓解组（均P<0.05）。缓解组、发作组FEV1%、FEV1/FVC、DLCO均低于对照组（均P<0.05）；发作组FEV1%、FEV1/FVC、DLCO均低于缓解组（均P<0.05）。Pearson相关性分析显示，miR-9-5p、SOCS5表达水平与Th2、CRP、IgE、WBC水平呈正相关，与Th1水平、Th1/Th2、FEV1%、FEV1/FVC、DLCO呈负相关（均P<0.05）。多因素logistic回归分析结果显示，高表达水平miR-9-5p（OR=2.203，95%CI：1.046～4.640）、SOCS5（OR=2.034，95%CI：1.065～3.844）及低Th1/Th2（OR=4.855，95%CI：2.217～10.633）均是哮喘控制水平不良的独立危险因素（均P<0.05）。结论　支气管哮喘患儿miR-9-5p、SOCS5表达水平高，且与Th1/Th2平衡有关。

关键词: 支气管哮喘, miR-9-5p, SOCS5, Th1/Th2平衡

Abstract:

Objective　To explore the expression levels of miR-9-5p and SOCS5 in the peripheral blood of children with bronchial asthma and their relationship with the Th1/Th2 balance. Methods　A total of 99 children with bronchial asthma who were admitted to Tongchuan maternal and child health hospital from June 2021 to June 2023 were selected as the study subjects. According to the control status of wheezing, the children were divided into the attack group (42 cases) and the remission group (57 cases). At the same time, 52 children who had no history of lung disease, wheezing, allergies, respiratory tract infections and were age-matched were selected from the pediatric ward as the control group. There were 22 boys and 20 girls in the attack group, aged (8.30±1.42) years. There were 30 boys and 27 girls in the remission group, aged (8.57±1.21) years. There were 32 boys and 20 girls in the control group, aged (8.23±1.36) years. The expression levels of miR-9-5p and SOCS5 were compared between the three groups, as well as the levels of helper T cells (Th) 1 and Th2, Th1/Th2 ratio, C-reactive protein (CRP), white blood cell count (WBC), immunoglobulin E (IgE), and pulmonary function indicators [percentage of forced expiratory volume in the first second as a percentage of predicted value (FEV1%), forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC), and carbon monoxide diffusion capacity (DLCO)]. Analysis of variance, SNK-q test, and χ² test were used for statistical analysis. Using Pearson correlation analysis, the relationships between the expression levels of miR-9-5p and SOCS5 and various indicators were investigated. Multivariate logistic regression analysis was used to investigate the influencing factors of poor asthma control in children. Results　The expression levels of miR-9-5p and SOCS5 in both the remission group and the attack group were higher than those in the control group (all P<0.05); the expression levels of miR-9-5p and SOCS5 in the attack group were higher than those in the remission group (both P<0.05). The levels of Th1 and Th1/Th2 in the remission group and the attack group were both lower than those in the control group, while the levels of Th2 were higher than those in the control group (all P<0.05); the levels of Th1 and Th1/Th2 in the attack group were both lower than those in the remission group, and the level of Th2 was higher than that in the remission group (all P<0.05). The levels of CRP, WBC and IgE in both the remission group and the attack group were higher than those in the control group (all P<0.05); the levels of CRP, WBC and IgE in the attack group were higher than those in the remission group (all P<0.05). The FEV1%, FEV1/FVC and DLCO values in the remission group and the attack group were all lower than those in the control group (all P<0.05); the FEV1%, FEV1/FVC and DLCO values in the attack group were all lower than those in the remission group (all P<0.05). The Pearson correlation analysis showed that the expression levels of miR-9-5p and SOCS5 were positively correlated with the levels of Th2, CRP, IgE, and WBC, and negatively correlated with the levels of Th1, Th1/Th2, FEV1%, FEV1/FVC, and DLCO (all P<0.05). The results of the multivariate logistic regression analysis showed that high expression levels of miR-9-5p (OR=2.203, 95%CI: 1.046-4.640), SOCS5 (OR=2.034, 95%CI: 1.065-3.844), and low Th1/Th2 ratio (OR=4.855, 95%CI: 2.217-10.633) were all independent risk factors for poor asthma control (all P<0.05). Conclusion　The expression levels of miR-9-5p and SOCS5 are high in children with bronchial asthma, and they are related to the Th1/Th2 balance.

Key words: Bronchial asthma, , miR-9-5p, , SOCS5, , Th1/Th2 balance

李惠芳韩玲样李庆华.

支气管哮喘患儿外周血miR-9-5p、SOCS5表达水平及与Th1/Th2平衡的关系 [J]. 国际医药卫生导报, 2025, 31(13): 2186-2191.

Li Huifang, Han Lingxiang, Li Qinghua.

Expression levels of miR-9-5p and SOCS5 in peripheral blood of children with bronchial asthma and their relationship with Th1/Th2 balance [J]. International Medicine and Health Guidance News, 2025, 31(13): 2186-2191.

参考文献

[1]Pijnenburg MW, Fleming L. Advances in understanding and reducing the burden of severe asthma in children[J]. Lancet Respir Med, 2020, 8(10):1032-1044. DOI: 10.1016/S2213-2600(20)30399-4.

[2]Harb H, Stephen-Victor E, Crestani E, et al. A regulatory T cell Notch4-GDF15 axis licenses tissue inflammation in asthma[J]. Nat Immunol, 2020, 21(11):1359-1370. DOI: 10.1038/s41590-020-0777-3.

[3]Keil TWM, Baldassi D, Merkel OM. T-cell targeted pulmonary siRNA delivery for the treatment of asthma[J]. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2020, 12(5):e1634. DOI: 10.1002/wnan.1634.

[4]ElKashef SMMAE, Ahmad SE, Soliman YMA, et al. Role of microRNA-21 and microRNA-155 as biomarkers for bronchial asthma[J]. Innate Immun, 2021, 27(1):61-69. DOI: 10.1177/1753425920901563.

[5]Chen ML, Hong CG, Yue T, et al. Inhibition of miR-331-3p and miR-9-5p ameliorates Alzheimer's disease by enhancing autophagy[J]. Theranostics, 2021, 11(5):2395-2409. DOI: 10.7150/thno.47408.

[6]Wang J, Wang B, Ren H, et al. miR-9-5p inhibits pancreatic cancer cell proliferation, invasion and glutamine metabolism by targeting GOT1[J]. Biochem Biophys Res Commun, 2019, 509(1):241-248. DOI: 10.1016/j.bbrc.2018.12.114.

[7]Zhang M, Liu S, Chua MS, et al. SOCS5 inhibition induces autophagy to impair metastasis in hepatocellular carcinoma cells via the PI3K/Akt/mTOR pathway[J]. Cell Death Dis, 2019, 10(8):612. DOI: 10.1038/s41419-019-1856-y.

[8]中华医学会儿科学分会呼吸学组,«中华儿科杂志»编辑委员会.儿童支气管哮喘诊断与防治指南(2016年版)[J].中华儿科杂志,2016,54(3):167-181.DOI:10.3760/cma.j.issn.0578-1310.2016.03.003.

[9]Yue P, Jing L, Zhao X, et al. Down-regulation of taurine-up-regulated gene 1 attenuates inflammation by sponging miR-9-5p via targeting NF-κB1/p50 in multiple sclerosis[J]. Life Sci, 2019, 233:116731. DOI: 10.1016/j.lfs.2019.116731.

[10]Xian X, Cai LL, Li Y, et al. Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression[J]. J Nanobiotechnology, 2022, 20(1):122. DOI: 10.1186/s12951-022-01332-w.

[11]Jin Z, Ren J, Qi S. Exosomal miR-9-5p secreted by bone marrow-derived mesenchymal stem cells alleviates osteoarthritis by inhibiting syndecan-1[J]. Cell Tissue Res, 2020, 381(1):99-114. DOI: 10.1007/s00441-020-03193-x.

[12]Yi J, Gao ZF. MicroRNA-9-5p promotes angiogenesis but inhibits apoptosis and inflammation of high glucose-induced injury in human umbilical vascular endothelial cells by targeting CXCR4[J]. Int J Biol Macromol, 2019, 130:1-9. DOI: 10.1016/j.ijbiomac.2019.02.003.

[13]Wang F, Chang S, Li J, et al. Lithium alleviated spinal cord injury (SCI)-induced apoptosis and inflammation in rats via BDNF-AS/miR-9-5p axis[J]. Cell Tissue Res, 2021, 384(2):301-312. DOI: 10.1007/s00441-020-03298-3.

[14]王明伟,王善涛,房有福.SOCS5基因多态性与哮喘患儿治疗效果及肺功能的关系研究[J].检验医学与临床,2023,20(17):2510-2514,2519.DOI:10.3969/j.issn.1672-9455.2023.17.012.

[15]Song W, Chen Y, Zhu G, et al. Exosome-mediated miR-9-5p promotes proliferation and migration of renal cancer cells both in vitro and in vivo by targeting SOCS4[J]. Biochem Biophys Res Commun, 2020, 529(4):1216-1224. DOI: 10.1016/j.bbrc.2020.06.114.

[16]Hu X, Chi Q, Wang D, et al. Hydrogen sulfide inhalation-induced immune damage is involved in oxidative stress, inflammation, apoptosis and the Th1/Th2 imbalance in broiler bursa of Fabricius[J]. Ecotoxicol Environ Saf, 2018, 164:201-209. DOI: 10.1016/j.ecoenv.2018.08.029.

[17]Asayama K, Kobayashi T, D'Alessandro-Gabazza CN, et al. Protein S protects against allergic bronchial asthma by modulating Th1/Th2 balance[J]. Allergy, 2020, 75(9):2267-2278. DOI: 10.1111/all.14261.

[18]Burt P, Peine M, Peine C, et al. Dissecting the dynamic transcriptional landscape of early T helper cell differentiation into Th1, Th2, and Th1/2 hybrid cells[J]. Front Immunol, 2022, 13:928018. DOI: 10.3389/fimmu.2022.928018.

[19]Aleebrahim-Dehkordi E, Molavi B, Mokhtari M, et al. T helper type (Th1/Th2) responses to SARS-CoV-2 and influenza A (H1N1) virus: from cytokines produced to immune responses[J]. Transpl Immunol, 2022, 70:101495. DOI: 10.1016/j.trim.2021.101495.

[20]Shang Q, Yu X, Sun Q, et al. Polysaccharides regulate Th1/Th2 balance: a new strategy for tumor immunotherapy[J]. Biomed Pharmacother, 2024, 170:115976. DOI: 10.1016/j.biopha.2023.115976.