Exploring mechanism of cardiac function decreasing in patients with ankylosing spondylitis based on Keap1-Nrf2-ARE signaling pathway / 中国免疫学杂志

ABSTRACT

Objective:To explore the mechanism of cardiac function decreasing in patients with ankylosing spondylitis based on Keap1-Nrf2-ARE signaling pathway .Methods:Experiment group included 140 ankylosing spondylitis ( AS) patients and control group included 60 healthy individuals .Echocardiography ( UCG) was used to detect cardiac function parameters .Enzyme-linked immunosor-bent assay(ELISA) was adopted to determine serum proteins ,oxidative stress indicators and cytokines .Erythrocyte sedimentation and plasma C reactive protein ,immunoglobulin were detected with Westergren method and Hitachi 7060 automatic biochemical analyzer re-spectively.Results:(1)Compared with the normal control group , character of AS group in active stage:cardiac function parameters(E peak,EF,E/A),antioxidant indicators(SOD,CAT,TAOC),cytokines(IL-4,IL-10)decreased (P<0.01 or P<0.05 all).A peak, Keap1,Nrf2,oxidation index(ROS,RNS,MDA),cytokines(IL-1,TNF-α),inflammatory indicators(ESR,CRP)increased(P<0.01 or P<0.05 all).(2)Compared with the normal control group, character of AS group in stable stage: cardiac function parameters(E peak,E/A),Keap1,antioxidant indicators(SOD,CAT,TAOC),cytokines(IL-4,IL-10)decreased (P<0.01 or P<0.05 all).A peak, Nrf2,oxidation index(ROS,RNS,MDA),cytokines(TNF-α),inflammatory indicators(ESR,CRP) increased(P<0.01 or P<0.05 all).(3)Compared with AS group in stable stage , character of AS group in active stage:cardiac function parameters(E peak,EF,E/A),antioxidant indicators(SOD,TAOC),cytokines(IL-10)decreased (P<0.01 or P<0.05 all).Keap1,Nrf2,oxidation index(ROS, RNS,MDA),cytokines(IL-1β,TNF-α),inflammatory indicators(ESR,CRP),clinical evaluation indicators (VAS,BASDAI,BASFI, BASMI,BAS-G)increased(P<0.01 or P<0.05 all).(4)Compared with AS patients with normal Keap1 or Nrf2 of peripheral blood, A peak increased while E peak and E/A decreased in AS patients with abnormal Keap1 or Nrf2 of peripheral blood (P<0.01 or P<0.05).(5)Spearman correlation analysis showed:AS parameters of cardiac function in patients with E peak and antioxidant indicators (SOD,CAT,TAOC),cytokines(IL-4,IL-10)showed significant positive correlation.E peak and Keap1, Nrf2,oxidation index(ROS, RNS,MDA),cytokines(IL-1β,TNF-α),inflammatory indicators(ESR,CRP),clinical evaluation indicators (VAS,BASDAI,BASFI, BASMI,BAS-G),IgG,course of the disease were significantly negatively correlated .A peak and Nrf2,oxidation index ( ROS,RNS, MDA) ,cytokines ( IL-1β,TNF-α) ,clinical evaluation indicators , Palpitation showed significant positive correlation .A peak and antiox-idant indicators(SOD,CAT,TAOC),cytokines(IL-4,IL-10)were significantly negatively correlated .E/A and Keap1,antioxidant indi-cators(SOD,CAT,TAOC),cytokines(IL-4,IL-10)showed significant positive correlation.E/A and oxidation index(ROS,RNS, MDA) ,cytokines ( TNF-α) ,cxcinical evaluation indicators ,course of the disease were significantly negatively correlated .EF and course of the disease were significantly negatively correlated .FS and Keap1 showed significant negative correlation .Conclusion:Cardiac func-tion decreasing in patients with ankylosing spondylitis is 33.56%.The characteristic performance is that E peak , E/A decreased while A peak increased.E peak,E/A and antioxidant indicators ,anti-inflammatory cytokines show significant positive correlation .E peak,E/A and Keap1,oxidation index,pro-inflammatory cytokines,inflammatory indicators are significantly negatively correlated .A peak and Keap1,oxidation index ,pro-inflammatory cytokines show significant positive correlation .A peak and antioxidant indicators ,anti-inflam-matory cytokines are significantly negatively correlated .The rising of Keap1 expression cause activate the Keap 1-Nrf2-ARE signaling pathway .After the signaling pathway is activated ,the body's antioxidant ability decreased , pro-inflammatory cytokines imbalanced , in-flammation index increased .When the body is long be in unbalance condition , the number of abnormal immune complex deposition in-creased.In the end,the result is that AS is caused and cardiac function is decreased .