[1]张兆明,陈素丽,姬 玉,等.NOD1mRNA 调节Th1/Th2 和Treg/Th17 细胞因子在肺结核中的免疫机制及预后价值研究[J].现代检验医学杂志,2023,38(06):23-29.[doi:10.3969/j.issn.1671-7414.2023.06.005]
　ZHANG Zhaoming,CHEN Suli,JI Yu,et al.Study on the Immunological Mechanism and Prognostic Value of NOD1 mRNA Regulating Th1/Th2 and Treg/Th17 Cytokines in Pulmonary Tuberculosis[J].Journal of Modern Laboratory Medicine,2023,38(06):23-29.[doi:10.3969/j.issn.1671-7414.2023.06.005]
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NOD1mRNA 调节Th1/Th2 和Treg/Th17 细胞因子在肺结核中的免疫机制及预后价值研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年06期
页码:
23-29
栏目:
论著
出版日期:
2023-11-15

文章信息/Info

Title:
Study on the Immunological Mechanism and Prognostic Value of NOD1 mRNA Regulating Th1/Th2 and Treg/Th17 Cytokines in Pulmonary Tuberculosis
文章编号:
1671-7414（2023）06-023-07
作者:
张兆明; 陈素丽; 姬 玉; 李雪燕; 田 月
（昌吉市人民医院医学检验科，新疆昌吉 831100）
Author(s):
ZHANG Zhaoming;  CHEN Suli;  JI Yu;  LI Xueyan;  TIAN Yue
（Department of Medical Laboratory， Changji People’s Hospital，Xinjiang Changji 831100，China）
关键词:
肺结核; 核苷酸结合寡聚化结构域1; 辅助性T 细胞1; 辅助性T 细胞2; 辅助性T 细胞17; 调节性T 细胞
分类号:
R521；R392.11
DOI:
10.3969/j.issn.1671-7414.2023.06.005
文献标志码:
A
摘要:
目的 探究肺结核 (tuberculosis，TB) 患者核苷酸结合寡聚化结构域1(nucleotide binding oligomerizationdomain1，NOD1）表达水平与辅助性T 细胞1(Th1)/ 辅助性T 细胞2(Th2), 辅助性T 细胞17(Th17) / 调节性T 细胞(regulatoryT cell，Treg ) 平衡的相关性，分析NOD1 mRNA 是否通过调节Th1/Th2，Treg/Th17 的平衡参与肺结核细胞免疫进展过程。方法 运用病例对照研究，收集2021 年6 月～ 2022 年7 月昌吉市人民医院结核病门诊收治的肺结核患者50 例作为肺结核组，同期健康体检者50 例作为对照组。所有病例均标准抗结核治疗6 个月，利用实时荧光定量聚合酶链式反应(qPCR) 法检测患者抗结核治疗前后外周血单个核细胞NOD1 基因的表达，酶联免疫吸附试验（ELISA）法检测血清Th1/Th2 和Th17/Treg 的细胞因子γ- 干扰素（interferon-γ，IFN-γ）、白细胞介素-4（IL-4）、白细胞介素-10（IL-10）和白细胞介素-17（IL-17）的表达水平。将抗结核治疗前后NOD1 与细胞因子IFN-γ，IL-4，IL-10 和IL-17 的动态变化进行相关性比较。运用多因素COX 回归分析影响肺结核患者短期预后的危险因素。结果 与对照组比较，肺结核组NOD1（10.87±5.29 vs 0.95±0.44），IL-4（17.23±4.77pg/ml vs 10.44±0.59pg/ml） 和IL-10（29.17±2.07pg/ml vs24.17±2.88pg/ml）表达水平均升高，差异具有统计学意义(t=44.86，-9.97，-9.89，均P<0.05)；肺结核组IFN-γ（3.91±0.52pg/ml）和IL-17[28.93（27.57~31.03）pg/ml] 表达水平均低于对照组[5.40±0.36pg/ml，33.35（29.77~35.10）pg/ml]，差异有统计学意义（t=16.58，Z=-5.79，均P<0.05)。与治疗前相比，治疗3 个月NOD1，IL-4 ，IL-10 和6 个月的表达水平显著下降，差异具有统计学意义（t=-17.03，2.46，5.51，-26.51，9.47，10.13，均P<0.05)；与治疗前相比，IFN-γ 和IL-17治疗3 个月和6 个月表达水平显著升高，差异有统计学意义(t=-5.28，-3.41，-13.81，-4.34，均P<0.05)；所有病例接受抗结核治疗后效果良好，治疗6 个月后与健康对照组比较，差异均无统计学意义(t=-1.01~1.73，均P>0.05）。Pearson相关性分析表明，NOD1 水平与IFN-γ，IL-10 水平呈正相关（r=0.514，0.421，P<0.05）, 与IL-4 水平呈负相关（r=-0.363，P<0.05），与IL-17 水平无明显相关性（r=0.125，P>0.05）。多因素COX 回归分析结果显示，NOD1mRNA 的表达≥ 10.87（OR=-0.923，P=0.040）和IFN-γ ≥ 3.90(OR=0.820，P=0.038) 的高表达是影响肺结核患者短期预后的危险因素。结论 NOD1 的表达水平与Th1/Th2，Treg/Th17 的平衡具有相关性，随着患者治疗的好转，NOD1 的表达是降低的，并且可能通过调节Th1/Th2，Treg/Th17 的平衡参与肺结核患者细胞免疫进展过程，但具体的变化机制还需要进一步研究。NOD1mRNA 和IFN-γ 的高表达，二者共同影响肺结核患者的短期预后。有望成为评估肺结核患者短期预后的危险因素。
Abstract:
Objective To explore the correlation between the expression level of nucleotide binding oligomerization domain 1 (NOD1) and the balance of helper T cell 1 (Th1)/helper T cell 2 (Th2) and helper T cell 17 (Th17)/regulatory T cell (Treg) in patients with pulmonary tuberculosis, and analyze whether NOD1 mRNA participates in the progression of pulmonary tuberculosis by regulating the balance of Th1/Th2 and Treg/Th17. Methods A case-control study was conducted to collect 50 cases of pulmonary tuberculosis patients admitted to the tuberculosis clinic of Changji People’s Hospital from June 2021 to July 2022, and 50 cases of health checkups in the same period served as controls. All cases were treated with standard anti-tuberculosis therapy for 6 months. The expression of NOD1 gene in peripheral blood mononuclear cells of patients before and after anti-tuberculosis therapy was detected using real-time quantitative PCR (qPCR) method. Expression levels of interferon-γ (IFN-γ), IL-4, IL-10, and IL-17, which belong to the cytokine IFN of serum Th1/Th2 and Th17/Treg, were detected using enzyme-linked immunosorbent assay (ELISA) method. The correlation between NOD1 and the dynamic changes of cytokines IFN-γ, IL-4, IL-10 and IL-17 before and after anti-tuberculosis treatment were compared. Multivariate COX regression analysis was used to analyze the risk factors affecting the short-term prognosis of patients with pulmonary tuberculosis. Results Compared with the control group, the expression levels of NOD1 (10.87 ± 5.29 vs 0.95 ± 0.44), IL-4 (17.23±4.77pg/ml vs 10.44±0.59pg/ml), and IL-10 (29.17 ± 2.07pg/ml vs 24.17 ± 2.88pg/ml) in the pulmonary tuberculosis group were higher than those in the control group, with statistical significance (t=44.86, -9.97, -9.89, all P<0.05). The expression levels of IFN-γ (3.91±0.52pg/ml）and IL-17 [28.93(27.57~31.03)pg/ml] in the pulmonary tuberculosis group were lower than those in the control group [5.40±0.36pg/ml, 33.35(29.77~35.10)pg/ml], with statistically significant differences (t=16.58, Z=-5.79, all P<0.05). Compared with before treatment, the expression levels of NOD1, IL-4 and IL-10 significantly decreased at 3 months and 6 months after treatment, and the differences were statistically significant (t=-17.03, 2.46, 5.51, -26.51, 9.47, 10.13, all P<0.05). Compared with IFN-γ and IL-17 before treatment, the expression levels of IFN-γ and IL-17 significantly increased after 3 and 6 months of treatment, with statistically significant differences (t=-5.28, -3.41, -13.81, -4.34, all P<0.05). All cases which received anti tuberculosis treatment showed good results, in which there was no statistically significant difference compared to the healthy control group after 6 months of treatment (t=-1.01~1.73, all P>0.05). Pearson correlation analysis shows that NOD1 levels were positively associated with the level of IFN-γ and IL-10 (r=0.514, 0.421, all P<0.05), and negatively correlated with the level of IL-4 (r=-0.363, P<0.05), but not significantly correlated with the level of IL-17 (r=0.125, P>0.05). The results of multivariate COX regression analysis showed that the expression of NOD1 mRNA was ≥ 10.87 (OR=-0.923, P=0.040) and IFN-γ ≥ 3.90 (OR=0.820, P=0.038), suggesting high expression of NOD1 mRNA and IFN-γ were risk factors affecting the short-term prognosis of pulmonary tuberculosis patients. Conclusion The expression level of NOD1 was correlated with the balance of Th1/Th2 and Treg/Th17. With the improvement of patient treatment, the expression of NOD1 decreases. These results showed that NOD1 may participate in the cellular immune progression of pulmonary tuberculosis patients by regulating the balance of Th1/Th2 and Treg/Th17. However, the specific mechanism of changes still needs further research. High expression of both NOD1 mRNA and IFN-γ jointly affect the short-term prognosis of patients with pulmonary tuberculosis, which may be expected to become risk factors for evaluating the short-term prognosis of patients with pulmonary tuberculosis.

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备注/Memo

备注/Memo:
基金项目：新疆昌吉州科技计划项目（2022110493）：NOD1 调节Th1/Th2/Treg/Th17 细胞因子在肺结核免疫中的作用和机制研究。
作者简介：张兆明（1978-），男，本科，副主任检验师，研究方向：感染免疫相关研究，E-mail：308754557@qq.com。
通讯作者：田 月（1987-），女，硕士，主管检验师，研究方向：血液免疫相关研究，E-mail：422971599@qq.com。
更新日期/Last Update: 2023-11-15