Th17/Treg细胞比例、诱导型一氧化氮合酶基因多态性与慢性阻塞性肺疾病患者脏腑虚损的相关性研究

Correlation of Th17/Treg cell ratio and inducible NO synthase gene polymorphism with Zang-fu deficiency in patients with chronic obstructive pulmonary diseases

摘要:

目的 探讨辅助性T细胞17/调节性T细胞（Th17/Treg）细胞比例、诱导型一氧化氮合酶（iNOS）基因多态性与慢性阻塞性肺疾病（COPD）患者脏腑虚损状况的相关性。方法 选取2017年1月—2020年1月新疆维吾尔自治区中医医院收治的130例COPD稳定期患者，根据患者疾病所属中医证型分为肺脾气虚组67例和肺肾气虚组63例，另选取同期该院健康体检者60例作为对照组。比较3组的肺功能，血清Th17、Treg及Th17/Treg细胞比例，iNOS基因型频率和等位基因频率。采用Pearson相关分析法分析Th17/Treg细胞比例与COPD脏腑虚损状况的相关性，多因素Logistic回归分析COPD脏腑虚损状况的影响因素。结果 肺脾气虚组和肺肾气虚组患者的用力肺活量（FVC）、第1秒用力呼气容积（FEV₁）低于对照组（P < 0.05），肺脾气虚组患者FVC、FEV₁大于肺肾气虚组（P < 0.05）。肺脾气虚组和肺肾气虚组患者的Th17、Th17/Treg高于对照组（P <0.05），Treg低于对照组（P < 0.05）；肺脾气虚组患者Th17、Th17/Treg水平低于肺肾气虚组（P < 0.05），Treg水平高于肺肾气虚组（P < 0.05）。Pearson相关分析结果显示，Th17/Treg与FVC、FEV₁、第1秒用力呼气容积占用力肺活量比值（FEV₁%）呈负相关（r =-0.407、-0.438和-0.504，均P <0.05），与肺脾气虚、肺肾气虚呈正相关（r =0.321和0.565，均P <0.05）。肺脾气虚组和肺肾气虚组患者GG基因型频率低于对照组（P < 0.05），TT基因型频率高于对照组（P < 0.05），T等位基因频率高于对照组（P <0.05）；肺脾气虚组GG基因型频率高于肺肾气虚组（P < 0.05），TT基因型频率低于肺肾气虚组（P < 0.05），T等位基因频率低于肺肾气虚组（P < 0.05）。Logistic回归分析结果显示，iNOS基因多态性中TT基因型［O^R =2.417（1.336，4.691），P <0.05）］是影响COPD脏腑虚损的独立危险因素。结论 Th17/Treg细胞比例与COPD患者脏腑虚损有明显相关性，且随着患者脏腑虚损进展，呈正相关，TT基因型是影响COPD脏腑虚损的独立危险因素。

Abstract:

Objective To investigate the effect of T Helper cell 17 (Th17)/Regulatory Cell (Treg) ratio and inducible NO synthase（iNOS）gene polymorphism on chronic obstructive pulmonary disease (COPD) patients with organ failure.Methods A total of 130 patients with COPD at stable stage admitted to our hospital from January 2017 to January 2020 were selected. According to the TCM syndromes of the patients' diseases, they were divided into the lung-spleen deficiency group (n = 67) and the lung-kidney deficiency group (n = 63), and 60 healthy people who underwent physical examination during the same period were selected as the control group. Lung function level, serum Th17, Treg, Th17/Treg cell ratio level, iNOS genotype frequency, and allele frequency were compared among the three groups. Pearson correlation analysis was used to analyze the correlation between Th17/Treg cell ratio and COPD Zang-fu-deficiency status, and multivariate Logistic regression was used to analyze the influencing factors of the deficiency of viscera in COPD.Results The FVC and FEV₁ in lung-spleen deficiency group and lung-kidney deficiency group were lower than those in control group (P < 0.05), and the FVC and FEV₁ in lung-spleen deficiency group were higher than those in lung-kidney deficiency group (P < 0.05). The levels of Th17 and Th17/Treg in lung-spleen deficiency group and lung-kidney deficiency group were higher than those in control group (P < 0.05), and the levels of Treg were lower than those in control group (P < 0.05). Th17 and Th17/Treg in lung-spleen deficiency group were lower than those in lung-kidney deficiency group (P < 0.05), and Treg was higher than that in lung-kidney deficiency group (P < 0.05). Pearson correlation analysis showed that Th17/Treg was negatively correlated with FVC, FEV₁ and FEV₁/FVC (r = -0.407, -0.438 and -0.504, all P < 0.05), and positively correlated with lung-spleen deficiency and lung-kidney deficiency (r = 0.321 and 0.565, all P < 0.05). The frequencies of GG genotype in lung-spleen deficiency group and lung-kidney deficiency group were lower than those in control group (P < 0.05), and TT genotype and T allele were higher than those in control group (P < 0.05). The frequencies of GG genotype in lung-spleen deficiency group were higher than those in lung-kidney deficiency group (P < 0.05), and the frequencies of TT genotype and T allele were lower than those in lung-kidney deficiency group (P < 0.05). Logistic regression analysis showed that the TT genotype of iNOS gene polymorphism was an independent risk factor for COPD deficiency of viscera [O^R =2.417 (1.336, 4.691), P < 0.05].Conclusion The ratio of Th17/Treg cells and iNOS gene polymorphism were significantly correlated with the status of Zang-fu deficiency in COPD patients, and were positively correlated with the progression of Zang-fu deficiency in COPD patients, among which TT genotype was an independent risk factor affecting the status of Zang-fu deficiency in COPD patients.