[Expression of LIAS and NRF2 in PBMCs from patients with silicosis and their correlation with silicosis].

Objective: To investigate the expression of lipoic acid synthase gene (LIAS) and nuclear factor-erythroid 2-related factor 2 gene (NRF2) in peripheral blood mononuclear cells (PBMCs) from patients with silicosis and their correlation with silicosis. Methods: A total of 45 healthy controls and 107 patients with silicosis were randomly selected in this study in May 2019. PBMCs were isolated from peripheral blood and NRF2 protein expression was detected by immunofluorescence. The mRNA levels of LIAS and NRF2 in PBMCs were determined by real-time PCR. The dose-response relationship beween LIAS and NRF2 mRNA expression levels and their association with silicosis were analyzed by restricted cubic spline (RCS) and logistic regression. Results: Compared with the control group, the number of monocytes in the case group was significantly increased, and the forced expiratory volume in the first second (FEV(1.0)) decreased, the difference was statistically significant (P<0.05) . The positive expression rate of NRF2 in PBMCs of silicosis patients in stage Ⅰ group was significantly higher than that in the control group, and the positive expression rate of NRF2 in silicosis patients in stageⅡ and Ⅲ groups was lower than that in silicosis patients in control group and stage Ⅰ group (P<0.01) . Results of RCS showed that there was a linear dose-response relationship between LIAS and NRF2 mRNA expression (overall correlation test, χ(2)=213.710, P<0.01; non-linear test, χ(2)=1.340, P=0.511) . There was a positive correlation between mRNA expression of LIAS and that of NRF2 (r=0.651, P<0.01) . The results of multivariate analysis showed that LIAS and NRF2 were increased the risk of incidence in silicosis patients with stageⅠ (OR=11.184, 4.332, P<0.05) and NRF2 was the protective factor in silicosis patients with stage Ⅱ and Ⅲ (OR=0.225, 0.208, P<0.05) after adjusting for potential confounding factors including age, education level, BMI and smoking. Conclusion: There is a linear dose-response relationship between the expression of LIAS and NRF2 mRNA in PBMCs of silicosis patients, LIAS and NRF2 are involved in the pathogenesis of silicosis.目的： 探讨矽肺患者外周血单个核细胞（PBMCs）中硫辛酸合成酶基因（LIAS）及核因子E2相关因子2基因（NRF2）的表达及其与矽肺的相关性。 方法： 于2019年5月，采用随机数字表法从正常健康体检人群中选取45人作为对照组，从矽肺患者中选取107人作为病例组。调查研究对象的基本资料并进行体格检查，采集外周血进行血细胞常规检测；采用免疫荧光法检测核因子E2相关因子2（NRF2）蛋白表达，实时荧光定量PCR测定LIAS、NRF2 mRNA表达水平。采用限制性三次样条（RCS）结合logistic回归分析PBMCs中LIAS、NRF2 mRNA表达水平的剂量-效应关系及其与矽肺的关联。 结果： 与对照组比较，病例组单核细胞数明显增高，第一秒用力呼气量（FEV(1.0)）降低，差异均有统计学意义（P<0.05）；壹期组矽肺患者PBMCs中NRF2阳性表达率明显高于对照组，贰期、叁期组矽肺患者NRF2阳性表达率均低于对照组及壹期组矽肺患者，差异均有统计学意义（P<0.01）。RCS结果显示，LIAS与NRF2 mRNA表达水平呈线性剂量-效应关系（总体关联性检验χ(2)=223.230，P<0.01；非线性检验χ(2)=1.340，P=0.511）。相关性分析显示，LIAS与NRF2 mRNA表达呈正相关（r=0.651，P<0.01）。多因素分析结果显示，调整潜在混杂因素（年龄、受教育程度、体质指数和吸烟）后，LIAS、NRF2与壹期矽肺发病风险的升高有关（OR=11.184、4.332，P<0.05）；在矽肺贰期、叁期患者中NRF2显示为矽肺发病的保护因素（OR=0.225、0.208，P<0.05）。 结论： 矽肺患者PBMCs中LIAS、NRF2 mRNA表达存在线性剂量-效应关系，并与矽肺发病相关。.