基于衰老相关分泌表型理论探讨老年慢性阻塞性肺疾病患者衰弱发生机制

Explore the mechanism of frailty in elderlychronic obstructive pulmonary disease patients based on senescence-associated secretory phenotype theory

目的基于衰老相关分泌表型(senescence-associated secretory phenotype,SASP)理论探讨老年慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者衰弱发生机制。方法采用前瞻性研究方法,选取2019年8月至2022年1月杭州市中医院收治的老年COPD患者130例,根据是否患有衰弱,将其分为衰弱组(n=75)和非衰弱组(n=55)。收集两组患者的一般临床资料,检测患者的血清细胞因子,如肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素(interleukin,IL)-1、IL-4、IL-6、IL-8、IL-10、IL-12及信号通路雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)、p53蛋白(p53 protein,p53)、核因子激活的B细胞κ-轻链(nuclearfactor-kappaB,NF-κB),采用单因素分析研究两组患者的上述因子浓度差异,采用多因素Logistic回归分析评估上述因子与衰弱的相关性,采用ROC曲线分析不同因子对衰弱的预测价值。结果单因素分析结果显示,衰弱组患者的血清中TNF-α、IL-1、mTOR、p53、NF-κB浓度高于非衰弱组,差异均有统计学意义(P<0.01)。多因素Logistic回归分析结果显示,TNF-α、IL-1、mTOR、p53、NF-κB可能是影响衰弱的因素(P<0.01)。受试者操作特征(receiver operating characteristic,ROC)曲线分析显示,TNF-α、IL-1、mTOR、p53、NF-kB对衰弱有一定的预测价值(P<0.01)。结论与p53-mTOR-NF-κB信号通路调节相关的以TNF-α、IL-1为主的SASP分泌可能是老年COPD患者发生衰弱的潜在机制。

Objective To explore the mechanism of frailty in elderly chronic obstructive pulmonary disease(COPD)patients with based on the theory of aging-related secretory phenotype(SASP).Methods Using prospective study method,130 elderly COPD patients admitted to Hangzhou Hospital of Traditional Chinese Medicine from August 2019 to January 2022 were selected and divided into frailty group(n=75)and non-frailty group(n=55).The general clinical data of both groups were collected.The levels of the serum cytokinestumor necrosis factor-α(TNF-α),inter-leukin(IL)-1 and signaling pathway factorsmammalian target of rapamycin(mTOR),p53 protein(p53)and nuclear factor-kappa B(NF-κB)in both groups were examined.Univariate factor analysis was used to study the difference in the concentrations of the measured factors between the two groups.Multivariate logistic regression analysis was used to evaluate the correlation between the measured factors and frailty.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of the cytokines and signaling pathway factors for frailty.Results Univariate analysis showed that the serum concentration of TNF-α,IL-1,mTOR,p53 and NF-κB in the frailty group were higher than those in the non-frailty group(P<0.01).Multivariate logistic regressionanalysis showed that the levels of TNF-α,IL-1,mTOR,p53 and NF-κB might be the factors leading frailty(P<0.01).ROC curve indicated that TNF-α,IL-1,mTOR,p53 and NFκB had certain predictive value for frailty(P<0.01).Conclusion SASP secretion dominated with TNF-α,IL-1 and regulated by p53-mTOR-NF-κB signaling pathway may be the potential mechan-ism of frailty in elderly COPD patients.