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中华肺部疾病杂志(电子版) ›› 2025, Vol. 18 ›› Issue (01) : 42 -47. doi: 10.3877/cma.j.issn.1674-6902.2025.01.007

论著

miR-150-5p 在青海地区结核分枝杆菌感染患者血清中的表达及意义
刘洪千1, 马琦2, 陈娟娟1, 王成军2, 武玲玲2, 冯喜英1,   
  1. 1. 810000 西宁,青海大学附属医院呼吸与危重症医学科
    2. 810000 西宁,青海大学附属医院临床医学院
  • 收稿日期:2024-10-30 出版日期:2025-02-25
  • 通信作者: 冯喜英
  • 基金资助:
    青海省科技厅课题(2022-ZJ-775)

Expression and clinical significance of miR-150-5p in the serum of patients with Mycobacterium tuberculosis infection in qinghai province

Hongqian Liu1, qi Ma2, Juanjuan Chen1, Chengjun Wang2, Lingling Wu2, Xiying Feng1,   

  1. 1. Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Qinghai University, Xining 810001,China
    2. Clinical School of Medicine, Affiliated Hospital of Qinghai University, Xining 810001, China
  • Received:2024-10-30 Published:2025-02-25
  • Corresponding author: Xiying Feng
引用本文:

刘洪千, 马琦, 陈娟娟, 王成军, 武玲玲, 冯喜英. miR-150-5p 在青海地区结核分枝杆菌感染患者血清中的表达及意义[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(01): 42-47.

Hongqian Liu, qi Ma, Juanjuan Chen, Chengjun Wang, Lingling Wu, Xiying Feng. Expression and clinical significance of miR-150-5p in the serum of patients with Mycobacterium tuberculosis infection in qinghai province[J/OL]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(01): 42-47.

目的

分析miR-150-5p 在青海地区结核分枝杆菌感染者血清中表达及与巨噬细胞极化关系。

方法

选择2022 年8 月至2023 年8 月青海大学附属医院、青海省第四人民医院经临床确诊的活动期肺结核(active lung tuberculosis,ALTB)35 例为观察组,结核潜伏感染(latent tuberculosis infection,LTBI)26 例为对照组,采用ELISA 法检测血清中白细胞介素10(interleukin-10,IL-10)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS);采用流式细胞术检测CD80、CD206 表达;采用qRT-PCR 试验检测miR-150-5p 表达。

结果

观察组miR-150-5p(28.11±5.41)、TNF-α(19.91±2.95)、iNOS(40.00±4.32)、CD-80(30.02±4.19)表达低于对照组miR-150-5p(38.37±3.51)、TNF-α(31.24±3.17)、iNOS(46.74±3.75)、CD-80(40.65±2.88)(P<0.05);观察组IL-10(100.92±5.83、81.05±9.34)、CD-206(56.33±6.10、33.72±7.65)表达高于对照组IL-10(81.05±9.34)、CD-206(33.72±7.65)(P=0.000)。 观察组miR-150-5p 表达与IL-10 呈正相关(r=0.385,P<0.05),与TNF-α、iNOS 无关;对照组miR-150-5p 表达与TNF、iNOS 呈正相关(r =0.558,P<0.05;r =0.509,P<0.05),与IL-10 不相关(r=-0.194,P>0.05)。 观察组miR-150-5p 表达与CD80 呈负相关(r =-0.395,P<0.05),与CD206 呈正相关(r=0.457, P<0.05);对照组miR-150-5p 表达与CD80 呈正相关(r =0.475,P<0.05),与CD206 呈负相关(r=-0.614, P<0.05)。

结论

miR-150-5p 在ALTB、LTBI 呈高表达,可为结核早期感染生物标志物。 结核感染状态下炎症因子TNF-α、IL-10、iNOS 高表达,ALTB、LTBI 中差异性表达可判断肺结核病情及疗效。 结核潜伏感染巨噬细胞向M1 型极化,活动性结核中巨噬细胞向M2 型极化。

Objective

To analyze the expression of miR-150-5p in the serum of Mycobacillus tuberculosis patients in Qinghai Province and its relationship with macrophage polarization.

Methods

Active lung tuberculosis patients diagnosed by clinical diagnosis in the Affiliated Hospital of Qinghai University and the Fourth People′s Hospital of Qinghai Province from August 2022 to August 2023 were selected.35 cases of tuberculosis (ALTB) were treated as observation group and 26 cases of latent tuberculosis infection (LTBI) as control group.Serum interleukin-10 (IL-10),tumor necrosis factor-α (TNF-α),inducible nitric oxide synthase(iNOS) were detected by ELISA; The expressions of CD80 and CD206 were detected by flow cytometry.The expression of miR-150-5p was detected by qRT-PCR assay.

Results

The expressions of miR-150-5p (28.11±5.41),TNF-α (19.91±2.95),iNOS (40.00±4.32),CD80 (30.02±4.19) in observation group were lower than those in control group (38.37±3.51) and TNF-α (31).24±3.17),iNOS (46.74±3.75),CD80 (40.65±2.88) (P<0.05); The expressions of IL-10 (100.92±5.83,81.05±9.34) and CD206 (56.33±6.10,33.72±7.65) in observation group were higher than those in control group (81.05±9.34) and CD206 (33.72±7.65)(P=0.000).The expression of miR-150-5p in the observation group was positively correlated with IL-10 (r =0.385, P<0.05),but had no correlation with TNF-α and iNOS.In control group,the expression of miR-150-5p was positively correlated with TNF and iNOS (r=0.558, P<0.05; r=0.509, P<0.05),was not correlated with IL-10 (r=-0.194,P>0.05).In the observation group,the expression of miR-150-5p was negatively correlated with CD80 (r=-0.395,P<0.05),and positively correlated with CD206 (r =0.457, P<0.05).In the control group,the expression of miR-150-5p was positively correlated with CD80 (r=0.475,P<0.05),and negatively correlated with CD206 (r =-0.614, P<0.05).

Conclusion

miR-150-5p is highly expressed in ALTB and LTBI,and may be a biomarker of early tuberculosis infection.In the state of tuberculosis infection,the expression of inflammatory factors TNF-α,IL-10 and iNOS is high,and the differential expression of ALTB and LTBI can judge the condition and curative effect of tuberculosis.Macrophages in latent tuberculosis infection were polarized to M1 type,and in active tuberculosis macrophages were polarized to M2 type.

表1 两组TB 患者TNF-α、IL-10、iNOS 结果比较(±s
图1 两组患者CD80 及CD206 表达代表性流式直方图 注:TB:活动性肺结核;LTBI:结核潜伏感染
表2 两组TB 患者miR-150-5p 及CD-80、CD-206 结果比较(±s
图2 miR-150-5p 与TNF-α、IL-10、iNOS 相关性A:观察组miR150-5p 与IL-10 相关性;B:对照组miR150-5p 与TNF-α 相关性;C:对照组miR150-5p 与INOS 相关性 注:IL-10 为白细胞介素10;TNF-α 为肿瘤坏死因子-α;iNOS 为诱导型一氧化氮合酶
表3 miR-150-5p 与TNF-α、IL-10、iNOS 相关性分析
图3 miR150-5p 表达与CD-80 CD-206 的相关性 A: 观察组miR150-5p 与CD-80、 CD-206 相关性;B:对照组miR150-5p 与CD-80、CD-206 相关性
表3 miR-150-5p 表达与CD-80、CD-206 相关性分析
1
Dominik Zenner,Daniella Brals,Joanna Nederby-Öhd,et al.Drivers determining tuberculosis disease screening yield in four European screening programmes: a comparative analysis[J].Eur Respir J,2023,62(4): 2202396.
2
Bagcchi S.WHO′s Global Tuberculosis Report 2022[J].Lancet Microbe,2023,4(1): e20.
3
Waganeh Sinshaw,Abebaw Kebede,Adane Bitew,et al.Prevalence of tuberculosis,multidrug resistant tuberculosis and associated risk factors among smear negative presumptive pulmonary tuberculosis patients in Addis Ababa,Ethiopia[J].BMC Infect Dis,2019,19(1): 641.
4
Francesca Wanda Basile,Sedona Sweeney,Maninder Pal Singh,et al.Uncertainty in tuberculosis clinical decision-making: An umbrella review with systematic methods and thematic analysis[J].PLOS Glob Public Health,2024,4(7): e0003429.
5
Tariro Christwish Mando,Charles Sandy,Addmore Chadambuka,et al.Tuberculosis cohort analysis in Zimbabwe: The need to strengthen patient follow-up throughout the tuberculosis care cascade[J].PLoS One,2023,18(11): e0293867.
6
Narjes Jafari,Saeid Abediankenari.Abediankenari,Role of microRNAs in immunoregulatory functions of epithelial cells[J].BMC Immunol,2024,25(1): 84.
7
Abualgasim Elgaili Abdalla,Awadh Alanazi,Khalid Omer Abdalla Abosalif,et al.MicroRNA-155,a double-blade sword regulator of innate tuberculosis immunity [J].Microb Pathog,2023,185:106438.
8
Evangeline Ann Daniel,Balakumaran Sathiyamani,Kannan Thiruvengadam,et al.MicroRNAs as diagnostic biomarkers for Tuberculosis: A systematic review and meta- analysis[J].Front Immunol,2022,13: 954396.
9
Piyush Agrawal,Aditya Upadhyay,Awanish Kumar.Kumar,microRNA as biomarkers in tuberculosis: a new emerging olecular diagnostic solution[J].Diagn Microbiol Infect Dis,2024,108(1): 116082.
10
Feng Sun,Jiangbo Li,Ling Cao,et al.Mycobacterium tuberculosis virulence protein ESAT-6 influences M1/M2 polarization and macrophage apoptosis to regulate tuberculosis progression[J].Genes Genomics,2024,46(1): 37-47.
11
Jagadeeswara Rao Muvva,Venkata Ramanarao Parasa,Maria Lerm,et al.Polarization of Human Monocyte-Derived Cells With Vitamin D Promotes Control of Mycobacterium tuberculosis Infection[J].Front Immunol,2019,10: 3157.
12
Rizk Sayad R Sarhan,Omnia Y Habashy,Raafat R Mohammed,et al.Active versus latent pulmonary tuberculosis: which one is the appropriate distinguishing biomarker[J].Monaldi Arch Chest Dis,2024,doi: 10.4081/monaldi.2024.2947.
13
Hyun Jin Cho,Yun-Ji Lim,Jhingook Kim,et al.Different macrophage polarization between drug-susceptible and multidrug-resistant pulmonary tuberculosis[J].BMC Infect Dis,2020,20(1): 81.
14
Zhangli Peng,Ling Chen,Hong Zhang.Serum proteomic analysis of Mycobacterium tuberculosis antigens for discriminating active tuberculosis from latent infection[J].J Int Med Res,2020,48(3):300060520910042.
15
Torres T,Brembilla NC,Langley RG,et al.Treatment of psoriasis with biologic and non-biologic targeted therapies in patients with latent tuberculosis infection or at risk for tuberculosis disease progression: Recommendations from a SPIN-FRT expert consensus[J].J Eur Acad Dermatol Venereol,2025,39(1): 52-69.
16
Rashad Abdul-Ghani,Asmaa Al-Awadi,Nuha Al-Aghbari,et al.Latent tuberculosis infection and diagnostic performance of the tuberculin skin test among type 2 diabetics in Sana′a city,Yemen[J].BMC Infect Dis,2024,24(1): 1005.
17
Monica Pagnoncelli,Marco Arosio,Alessandro Genovesi,et al.Performance of the T-SPOT.TB test in patients with indeterminate QuantiFERON-TB Gold Plus results: proposal for an algorithm for the diagnosis of Latent Tuberculosis Infection[J].Infez Med,2024,32(4): 525-531.
18
Antony M Rapulana,Thabo Mpotje,Omolara O Baiyegunhi,et al.Combined analysis of host IFN-γ,IL-2 and IP-10 as potential LTBI biomarkers in ESAT-6/CFP-10 stimulated blood[J].Front Mol Med,2024,4: 1345510.
19
Yuanchun Li,Zhengrong Yang,Qiping Ge,et al.Specific cytokines analysis Incorporating latency-associated antigens differentiates Mycobacterium tuberculosis infection status: an exploratory study[J].Infect Drug Resist,2024,17: 3385-3393.
20
Qingqing Shan,Yangke Li,Kun Yuan,et al.Distinguish active tuberculosis with an immune-related signature and molecule subtypes: a multi-cohort analysis[J].Sci Rep,2024,14(1):29564.
21
Chih-Jung Chang,Jhong-Ru Huang,Yen-Han Tseng,et al.Global cell-free DNA methylation in patients with active tuberculosis and tuberculosis contacts with latent tuberculosis infection[J].Diagn Microbiol Infect Dis,2025,111(1): 116559.
22
Joyita Banerjee,Swagata Roy,Yogita Dhas,et al.Senescenceassociated miR-34a and miR-126 in middle-aged Indians with type 2 diabetes[J].Clin Exp Med,2020,20(1): 149-158.
23
Daniel EA,Sathiyamani B,Thiruvengadam K,et al.miR-29 as diagnostic biomarkers for tuberculosis: a systematic review and meta-analysis[J].Front Public Health,2024,12: 1384510.
24
Zhicheng Sun,Xiaoyang Pang,Xiyang Wang,et al.Differential expression analysis of miRNAs in macrophage-derived exosomes in the tuberculosis-infected bone microenvironment [ J ].Front Microbiol,2023,14: 1236012.
25
Gwenda F Vasse,Mehmet Nizamoglu,Irene H Heijink,et al.Macrophage-stroma interactions in fibrosis: biochemical,biophysical,and cellular perspectives[J].J Pathol,2021,254(4): 344-357.
26
Xiangyi Kong,Jun Gao.Macrophage polarization:a key event in the secondary phase of acute spinal cord injury[J].J Cell Mol Med,2017,21(5): 941-954.
27
Chen S,Saeed AFUH,Liu Q,et al.Macrophages in immunoregulation and therapeutics[J].Signal Transduct Target Ther,2023,8(1):207.
28
Renhao Ni,Lingjing Jiang,Chaohai Zhang,et al.Biologic mechanisms of macrophage phenotypes responding to infection and the novel therapies to moderate inflammation[J].Int J Mol Sci,2023,24(9): 8358.
29
Malika Ali,Marcel Bonay,Valentin Vanhee,et al.Comparative effectiveness of 4 natural and chemical activators of Nrf2 on inflammation,oxidative stress,macrophage polarization,and bactericidal activity in an in vitro macrophage infection model[J].PLoS One,2020,15(6): e0234484.
30
Wang S,Cao M,Xu S,et al.Luteolin alters macrophage polarization to inhibit inflammation[J].Inflammation,2020,43(1): 95-108.
31
Alyson A Fiorillo,Christopher R Heier,Yu-Fang Huang,et al.Estrogen Receptor,Inflammatory,and FOXO Transcription Factors Regulate Expression of Myasthenia Gravis-Associated Circulating microRNAs[J].Front Immunol,2020,11: 151.
32
Sanjaya Kumar Sahu,Manish Kumar,Sohini Chakraborty,et al.MicroRNA 26a (miR-26a)/KLF4 and CREB-C/EBPβ regulate innate immune signaling,the polarization of macrophages and the trafficking of Mycobacterium tuberculosis to lysosomes during infection[J].PLoS Pathog,2017,13(5): e1006410.
33
Ruiying Wang,Zhifan Zhu,Shisheng Peng,et al.Exosome microRNA-125a-5p derived from epithelium promotes M1 macrophage polarization by targeting IL1RN in chronic obstructive pulmonary disease[J].Int Immunopharmacol,2024,137: 112466.
34
Ying Peng,Xian-Jin Wu,Xue-Jiao Ji,et al.Circular RNA circTRAPPC6B Enhances IL-6 and IL-1β Expression and Repolarizes Mycobacteria Induced Macrophages from M2- to M1-Like Phenotype by Targeting miR-892c-3p[J].J Interferon Cytokine Res,2023,43(6): 269-279.
35
Jun Lou,Yongli Wang,Zhimin Zhang,et al.MiR-20b inhibits mycobacterium tuberculosis induced inflammation in the lung of mice through targeting NLRP3[J].Exp Cell Res,2017,358(2):120-128.
36
Huang Z,Gao C,Chi X,et al.IL-37 Expression is Upregulated in Patients with Tuberculosis and Induces Macrophages Towards an M2-like Phenotype[J].Scand J Immunol,2015,82(4): 370-379.
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