结核分枝杆菌感染者外周血单个核细胞中肝激酶B1的表达及其与γ-干扰素的相关性

doi:10.19982/j.issn.1000-6621.20250097

摘要/Abstract

摘要：

目的: 分析结核分枝杆菌(Mycobacterium tuberculosis,MTB)感染者外周血单个核细胞(peripheral blood mononuclear cells,PBMC)中肝激酶B1(liver kinase B1,LKB1)基因表达水平及其与γ-干扰素(IFN-γ)水平的相关性。方法: 采用前瞻性研究方法,纳入2024年3—6月期间于西安市胸科医院住院的23例活动性肺结核患者作为肺结核组;纳入同期空军军医大学西京医院门诊诊断的20例结核分枝杆菌潜伏感染(latent tuberculosis infection,LTBI)者作为LTBI组;纳入同期于空军军医大学西京医院进行健康体检的20名健康体检者作为健康对照组。收集所有研究对象的外周血样本,分离出PBMC,比较各组PBMC中LKB1 mRNA表达情况、IFN-γ水平,分析LKB1基因表达水平与IFN-γ水平的相关性。结果: (1)肺结核组、LTBI组和健康对照组LKB1的相对表达量分别为0.529(0.304,0.964)、1.326(1.064,1.591)、0.949(0.732,1.396),差异有统计学意义(H=23.707,P<0.01)。肺结核组的LKB1 mRNA表达量明显低于健康对照组,差异有统计学意义(H=2.560,P=0.031),LTBI组的LKB1 mRNA表达量明显高于肺结核组,差异有统计学意义(H=-4.857,P<0.01)。(2)肺结核组患者外周血LKB1 mRNA相对表达水平与早期分泌抗原靶-6刺激的IFN-γ水平呈负相关(r=-0.647,P=0.001),与培养滤液蛋白-10刺激的IFN-γ水平也呈负相关(r=-0.435,P=0.038)。结论: 活动性肺结核患者PBMC中的LKB1基因呈低表达水平,且与IFN-γ的水平呈负相关。

关键词: 分枝杆菌,结核, 感染, 肝激酶B1, 基因表达, 干扰素γ

Abstract:

Objective: To investigate the expression level of liver kinase B1 (LKB1) gene in peripheral blood mononuclear cells (PBMCs) of Mycobacterium tuberculosis (MTB)-infected individuals and its correlation with interferon-γ (IFN-γ) levels. Methods: In this prospective study conducted between March and June 2024, we enrolled 23 patients with active pulmonary tuberculosis (PTB) hospitalized at Xi’an Chest Hospital, 20 individuals with latent tuberculosis infection (LTBI) diagnosed in the outpatient department of Xijing Hospital of Air Force Medical University, and 20 healthy individuals undergoing routine check-ups at the same hospital as the healthy control group. Peripheral blood samples were collected from all participants, and PBMCs were isolated. The mRNA expression levels of LKB1 and IFN-γ were compared across the three groups. The association between LKB1 expression and IFN-γ levels was assessed using correlation analysis. Results: (1) The relative expression levels of LKB1 in the PTB, LTBI, and healthy control groups were 0.529 (0.304, 0.964), 1.326 (1.064, 1.591), and 0.949 (0.732, 1.396), respectively. Statistically significant differences were observed among the three groups (H=23.707, P<0.01). LKB1 mRNA expression was markedly reduced in the PTB group compared with the healthy controls (H=2.560, P=0.031), while the LTBI group demonstrated a significantly elevated expression compared with the PTB group (H=-4.857, P<0.01). (2) In patients with PTB, the relative expression level of LKB1 mRNA in peripheral blood was inversely correlated with IFN-γ levels following stimulation with ESAT-6 antigen (r=-0.647, P=0.001) and CFP-10 antigen (r=-0.435, P=0.038). Conclusion: LKB1 expression is significantly downregulated in PBMCs of patients with active PTB and is inversely associated with IFN-γ levels, suggesting a potential role for LKB1 in modulating immune responses during MTB infection.

Key words: Mycobacterium tuberculosis, Infection, Liver kinase B1, Gene expression, Interferon-gamma

中图分类号:

魏潇芮, 于泽洋, 杨琨, 周柯, 黄芳, 刘昊, 白露, 刘家云. 结核分枝杆菌感染者外周血单个核细胞中肝激酶B1的表达及其与γ-干扰素的相关性[J]. 中国防痨杂志, 2025, 47(6): 779-784. doi: 10.19982/j.issn.1000-6621.20250097

Wei Xiaorui, Yu Zeyang, Yang Kun, Zhou Ke, Huang Fang, Liu Hao, Bai Lu, Liu Jiayun. Expression of liver kinase B1 in peripheral blood mononuclear cells of Mycobacterium tuberculosis-infected individuals and its correlation with interferon-γ[J]. Chinese Journal of Antituberculosis, 2025, 47(6): 779-784. doi: 10.19982/j.issn.1000-6621.20250097

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组别	例数	早期分泌抗原靶-6	培养滤液蛋白-10
肺结核组	23	86.0(29.0,194.0)	49.0(13.0,202.0)
结核分枝杆菌潜伏感染组	20	19.0(12.8,42.3)	7.5(3.3,29.5)
健康对照组	20	0.0(0.0,2.0)	0.0(0.0,1.0)

组别	例数	白细胞计数	单核细胞计数	淋巴细胞计数
肺结核组	23	9.58±3.18	0.86±0.30	1.34±0.29
结核分枝杆菌潜伏感染组	20	6.40±1.70	0.62±0.22	2.61±0.32
健康对照组	20	6.15±1.15	0.36±0.06	2.58±0.39