类风湿关节炎外周血BTLA及BMSCs内Nrf2信号通路相关基因表达与肺部感染的关系

Relationship between expressions of BTLA in peripheral blood, Nrf2 signaling pathways-related genes in BMSCs and pulmonary infection in patients with rheumatoid arthritis

目的 探究类风湿关节炎(RA)患者外周血B/T淋巴细胞衰减因子(BTLA)及骨髓间充质干细胞(BMSCs)内核因子E2-相关因子2(Nrf2)信号通路相关基因表达与肺部感染的关系。方法 选取2019年7月-2021年7月贵州航天医院收治的30例RA合并肺部感染患者为感染组,选取同期收治无肺部感染RA患者30例为未感染组。采集感染组患者痰液标本,分析病原菌分布情况;采用实时荧光定量逆转录聚合酶链式反应(RT-PCR)法检测BTLA、Nrf2、Keap1及ARE的mRNA表达量。结果 感染组患者分离病原菌36株,革兰阴性菌20株(55.56%)、革兰阴性菌11株(30.56%)、真菌5株(13.89%);感染组患者年龄、病程均大于未感染组(P<0.05),合并糖尿病占比高于未感染组(P<0.05);感染组患者白细胞介素-1(IL-1)、肿瘤坏死因子-α(TNF-α)、丙二醛(MDA)水平高于未感染组,感染组患者超氧化物歧化酶(SOD)水平、BTLA、Nrf2、Keap1及ARE的mRNA表达量低于未感染组(P<0.05);高龄、长病程、有糖尿病史均是RA合并肺部感染危险因素(P<0.05);Nrf2、Keap1及ARE mRNA表达量与MDA呈负相关(P<0.05),与SOD呈正相关(P<0.05)。结论 RA患者并发肺部感染与BTLA及Nrf2信号通路相关基因表达水平降低有关,外周血BTLA基因表达量缺失可加重患者炎症反应,BMSCs内Nrf2相关信号通路可负向调节患者氧化应激反应,损伤肺部组织,增加病原菌感染风险。

OBJECTIVE To explore the association of expressions of B/T lymphocyte attenuation factor(BTLA) in peripheral blood, nuclear factor E2-related factor 2(Nrf2) signaling pathways-related genes in bone marrow mesenchymal stem cells(BMSCs) with pulmonary infection in the patients with rheumatoid arthritis(RA). METHODS A total of 30 RA patients who were complicated with pulmonary infection and treated in Guizhou Aerospace Hospital from Jul 2019 to Jul 2021 were assigned as the infection group, meanwhile, 30 RA patients who did not have pulmonary infection were chosen as the no infection group. The sputum specimens were collected from the patients of the infection group, the distribution of pathogens was analyzed, the expression levels of BTLA, Nrf2, Keap1 and ARE mRNA were detected by means of real-time fluorescent quantitative reverse transcription polymerase chain reaction(RT-PCR). RESULTS Totally 36 strains of pathogens were isolated from the patients of the infection group, 20(55.56%) of which were gram-negative bacteria, 11(30.56%) were gram-negative bacteria, and 5(13.89%) were fungi. The age and course of disease of the infection group were significantly greater than those of the no infection group(P<0.05), the proportion of patients complicated with diabetes mellitus was significantly higher in the infection group than in the no infection group(P<0.05).The levels of interleukin-1(IL-1), tumor necrosis factor-α(TNF-α) and malonaldehyde(MDA) of the infection group were significantly higher than those of the no infection group, the superoxide dismutase(SOD) level and the expression levels of BTLA, Nrf2, Keap1 and ARE mRNA were significantly lower in the infection group than in the no infection group(P<0.05). The advanced age, long course of disease and history of diabetes mellitus were the risk factors for the pulmonary infection in the RA patients(P<0.05). The expression levels of Nrf2, Keap1 and ARE mRNA were negatively correlated with MDA(P<0.05) and were positively correlated with SOD(P<0.05). CONCLUSION The pulmonary infection in the RA patients is associated with the decline of expression levels of BTLA and Nrf2 signaling pathway-related genes. The loss of BTLA gene in peripheral blood may aggravate the inflammatory response, Nrf2-related signaling pathway in BMSCs can negatively regulate the oxidative stress response, cause the damage of lung tissue and increase the risk of infection.