关键词: 微小RNA-146a-5p, 微小RNA -146b-5p, Toll样受体4, 核因子-κB, 大动脉粥样硬化型脑梗死, 预后

Abstract:

Objective To investigate the expressions of serum miR-146a-5p and miR-146b-5p in patients with large-artery atherosclerosis（LAA）type cerebral infarction and their relationship with Toll-like receptor 4（TLR4）/nuclear factor-kappa B（NF-κB） signaling pathway and prognosis. Methods From June 2021 to September 2023，97 patients with LAA type cerebral infarction（LAA type cerebral infarction group） and 70 healthy subjects （healthy control group） were enrolled from Yantai Yeda Hospital. The clinical data were collected，and the expressions of TLR4 mRNA and NF-κB mRNA in peripheral blood mononuclear cells（PMBC）were determined. The expression of miR-146a-5p and miR-146b-5p in serum were determined. According to the modified Rankin scale（mRS） score of 90 d after intravenous thrombolysis，they were classified into good prognosis group（62 cases） and poor prognosis group（35 cases）. Pearson correlation analysis was used to evaluate the correlation between various indicators. Using Logistic regression analysis，the influencing factors of poor prognosis in patients with LAA type cerebral infarction were evaluated. The efficacy of serum miR-146a-5p and miR-146b-5p in predicting poor prognosis of LAA type cerebral infarction was evaluated using receiver operating characteristic（ROC） curve. Results The relative expression levels of serum miR-146a-5p and miR-146b-5p in LAA type cerebral infarction group were lower than those in healthy control group（P<0.001）. Compared with good prognosis group，the relative expression levels of serum miR-146a-5p and miR-146b-5p in poor prognosis group were decreased（P<0.001），while the relative expression levels of TLR4 mRNA and NF-κB mRNA in PBMC were increased（P<0.001）. The expression of serum miR-146a-5p and miR-146b-5p in patients with LAA type cerebral infarction was negatively correlated with the expressions of TLR4 mRNA and NF-κB mRNA in PBMC（P<0.001）. Increased National Institute of Health Stroke Scale（NIHSS）score at admission，increased infarction volume and decreased relative expression levels of miR-146a-5p and miR-146b-5p were risk factors for poor prognosis in LAA type cerebral infarction patients [odds ratios（OR） were 1.950，2.359，0.625 and 0.748，95% confidence intervals（CI） were 1.204-2.538，1.517-3.394，0.531-0.711 and 0.651-0.806，respectively，P<0.05]. The areas under curves （AUC） of single and combined determinations of serum miR-146a-5p and miR-146b-5p for predicting poor prognosis in LAA type cerebral infarction patients were 0.828，0.765 and 0.903，respectively. The AUC of combined determination with NIHSS score at admission and infarction volume was 0.945. Conclusions The low expression of serum miR-146a-5p and miR-146b-5p in patients with LAA type cerebral infarction is related to the activation of TLR4/NF-κB pathway and poor prognosis，which can be used for clinical diagnosis and treatment of LAA type cerebral infarction.

Key words: MicroRNA-146a-5p, MicroRNA-146b-5p, Toll-like receptor 4, Nuclear factor- kappa B signaling pathway, Large-artery atherosclerosis, Prognosis