风湿病与关节炎
風濕病與關節炎
풍습병여관절염
Rheumatism and Arthritis
2014年
7期
9-16
,共8页
刘健%齐亚军%郑力%万磊%曹云祥%孙玥%王芳
劉健%齊亞軍%鄭力%萬磊%曹雲祥%孫玥%王芳
류건%제아군%정력%만뢰%조운상%손모%왕방
脊柱炎,强直性%Keap1-Nrf2-ARE%肺功能%Keap1%Nrf2%氧化应激
脊柱炎,彊直性%Keap1-Nrf2-ARE%肺功能%Keap1%Nrf2%氧化應激
척주염,강직성%Keap1-Nrf2-ARE%폐공능%Keap1%Nrf2%양화응격
spondylitis,ankylosing%keap1-Nrf2-ARE%pulmonary function%Keap1%Nrf2%oxidative stress
目的:基于Keap1-Nrf2-ARE通路探讨强直性脊柱炎患者肺功能降低的机制。方法:选取120例强直性脊柱炎患者作为研究组,并从体检中心抽取60例健康人作为正常对照组。采用德国Jager MasterScreen自动肺功能检测仪测定两组肺功能参数[用力肺活量(FVC)、第1秒用力呼气容积(FEV1)、最大通气量(MVV)、最大呼气流量(PEF)、25%肺活量位的最大呼气流量(FEF25)、50%肺活量位的最大呼气流量(FEF50)、75%肺活量位的最大呼气流量(FEF75)];采用酶联免疫分析法(ELISA法)检测两组血清中通路蛋白[Kelch样ECH相关蛋白l(Keap1)、核因子NF-E2相关因子(Nrf2)]、氧化应激指标[丙二醛(MDA)、活性氧(ROS)、活性氮(RNS)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、总抗氧化能力(TAOC)]和细胞因子[白细胞介素(IL)-18、肿瘤坏死因子(TNF)-α、IL-4、IL-35]含量;采用魏氏法检测炎性指标红细胞沉降率(ESR);采用日立7060型全自动生化分析仪检测C-反应蛋白(CRP)、免疫球蛋白。结果:与正常对照组比较:①强直性脊柱炎患者FEV1、MVV、PEF、FEF50、FEF75值均显著降低(P<0.01或P<0.05);与强直性脊柱炎患者Keap1、Nrf2正常组比较,Keap1、Nrf2异常组FEV1、MVV、PEF、FEF50、FEF75值显著降低(P<0.05或P<0.01)。②强直性脊柱炎患者血清中Keap1、Nrf2、ROS、RNS、MDA值显著升高(P<0.01或P<0.05), SOD、CAT、TAOC值均显著降低(P<0.01或P<0.05)。③强直性脊柱炎患者IL-18、TNF-α、ESR、CRP值显著升高(P<0.01),IL-4、IL-35值显著降低(P<0.01或P<0.05)。④Spearman相关性分析显示,FEV1、MVV、PEF、FEF50、FEF75与SOD、CAT、TAOC、IL-4、IL-35呈正相关,与Keap1、Nrf2、ROS、RNS、MDA、IL-18、TNF-α、ESR、CRP、胸闷、气短、呼吸困难呈负相关(P<0.01或P<0.05)。结论:58.33%的强直性脊柱炎患者存在肺功能降低,表现为肺功能参数FEV1、MVV、PEF、FEF50、FEF75值均显著降低,以上肺功能参数与抗氧化指标、抑炎细胞因子呈正相关,与通路蛋白(Keap1、Nrf2)、氧化指标、致炎细胞因子、炎症指标呈负相关。Keap1、Nrf2表达上升,Keap1-Nrf2-ARE信号通路活化后,机体抗氧化能力下降,促使细胞因子失衡、炎症指标升高,导致免疫复合物异常沉积增多,在引起强直性脊柱炎发病的同时使肺组织或器官受损或破坏,最终出现肺功能降低。
目的:基于Keap1-Nrf2-ARE通路探討彊直性脊柱炎患者肺功能降低的機製。方法:選取120例彊直性脊柱炎患者作為研究組,併從體檢中心抽取60例健康人作為正常對照組。採用德國Jager MasterScreen自動肺功能檢測儀測定兩組肺功能參數[用力肺活量(FVC)、第1秒用力呼氣容積(FEV1)、最大通氣量(MVV)、最大呼氣流量(PEF)、25%肺活量位的最大呼氣流量(FEF25)、50%肺活量位的最大呼氣流量(FEF50)、75%肺活量位的最大呼氣流量(FEF75)];採用酶聯免疫分析法(ELISA法)檢測兩組血清中通路蛋白[Kelch樣ECH相關蛋白l(Keap1)、覈因子NF-E2相關因子(Nrf2)]、氧化應激指標[丙二醛(MDA)、活性氧(ROS)、活性氮(RNS)、超氧化物歧化酶(SOD)、過氧化氫酶(CAT)、總抗氧化能力(TAOC)]和細胞因子[白細胞介素(IL)-18、腫瘤壞死因子(TNF)-α、IL-4、IL-35]含量;採用魏氏法檢測炎性指標紅細胞沉降率(ESR);採用日立7060型全自動生化分析儀檢測C-反應蛋白(CRP)、免疫毬蛋白。結果:與正常對照組比較:①彊直性脊柱炎患者FEV1、MVV、PEF、FEF50、FEF75值均顯著降低(P<0.01或P<0.05);與彊直性脊柱炎患者Keap1、Nrf2正常組比較,Keap1、Nrf2異常組FEV1、MVV、PEF、FEF50、FEF75值顯著降低(P<0.05或P<0.01)。②彊直性脊柱炎患者血清中Keap1、Nrf2、ROS、RNS、MDA值顯著升高(P<0.01或P<0.05), SOD、CAT、TAOC值均顯著降低(P<0.01或P<0.05)。③彊直性脊柱炎患者IL-18、TNF-α、ESR、CRP值顯著升高(P<0.01),IL-4、IL-35值顯著降低(P<0.01或P<0.05)。④Spearman相關性分析顯示,FEV1、MVV、PEF、FEF50、FEF75與SOD、CAT、TAOC、IL-4、IL-35呈正相關,與Keap1、Nrf2、ROS、RNS、MDA、IL-18、TNF-α、ESR、CRP、胸悶、氣短、呼吸睏難呈負相關(P<0.01或P<0.05)。結論:58.33%的彊直性脊柱炎患者存在肺功能降低,錶現為肺功能參數FEV1、MVV、PEF、FEF50、FEF75值均顯著降低,以上肺功能參數與抗氧化指標、抑炎細胞因子呈正相關,與通路蛋白(Keap1、Nrf2)、氧化指標、緻炎細胞因子、炎癥指標呈負相關。Keap1、Nrf2錶達上升,Keap1-Nrf2-ARE信號通路活化後,機體抗氧化能力下降,促使細胞因子失衡、炎癥指標升高,導緻免疫複閤物異常沉積增多,在引起彊直性脊柱炎髮病的同時使肺組織或器官受損或破壞,最終齣現肺功能降低。
목적:기우Keap1-Nrf2-ARE통로탐토강직성척주염환자폐공능강저적궤제。방법:선취120례강직성척주염환자작위연구조,병종체검중심추취60례건강인작위정상대조조。채용덕국Jager MasterScreen자동폐공능검측의측정량조폐공능삼수[용력폐활량(FVC)、제1초용력호기용적(FEV1)、최대통기량(MVV)、최대호기류량(PEF)、25%폐활량위적최대호기류량(FEF25)、50%폐활량위적최대호기류량(FEF50)、75%폐활량위적최대호기류량(FEF75)];채용매련면역분석법(ELISA법)검측량조혈청중통로단백[Kelch양ECH상관단백l(Keap1)、핵인자NF-E2상관인자(Nrf2)]、양화응격지표[병이철(MDA)、활성양(ROS)、활성담(RNS)、초양화물기화매(SOD)、과양화경매(CAT)、총항양화능력(TAOC)]화세포인자[백세포개소(IL)-18、종류배사인자(TNF)-α、IL-4、IL-35]함량;채용위씨법검측염성지표홍세포침강솔(ESR);채용일립7060형전자동생화분석의검측C-반응단백(CRP)、면역구단백。결과:여정상대조조비교:①강직성척주염환자FEV1、MVV、PEF、FEF50、FEF75치균현저강저(P<0.01혹P<0.05);여강직성척주염환자Keap1、Nrf2정상조비교,Keap1、Nrf2이상조FEV1、MVV、PEF、FEF50、FEF75치현저강저(P<0.05혹P<0.01)。②강직성척주염환자혈청중Keap1、Nrf2、ROS、RNS、MDA치현저승고(P<0.01혹P<0.05), SOD、CAT、TAOC치균현저강저(P<0.01혹P<0.05)。③강직성척주염환자IL-18、TNF-α、ESR、CRP치현저승고(P<0.01),IL-4、IL-35치현저강저(P<0.01혹P<0.05)。④Spearman상관성분석현시,FEV1、MVV、PEF、FEF50、FEF75여SOD、CAT、TAOC、IL-4、IL-35정정상관,여Keap1、Nrf2、ROS、RNS、MDA、IL-18、TNF-α、ESR、CRP、흉민、기단、호흡곤난정부상관(P<0.01혹P<0.05)。결론:58.33%적강직성척주염환자존재폐공능강저,표현위폐공능삼수FEV1、MVV、PEF、FEF50、FEF75치균현저강저,이상폐공능삼수여항양화지표、억염세포인자정정상관,여통로단백(Keap1、Nrf2)、양화지표、치염세포인자、염증지표정부상관。Keap1、Nrf2표체상승,Keap1-Nrf2-ARE신호통로활화후,궤체항양화능력하강,촉사세포인자실형、염증지표승고,도치면역복합물이상침적증다,재인기강직성척주염발병적동시사폐조직혹기관수손혹파배,최종출현폐공능강저。
Objective:To investigate the mechanism of reduction of pulmonary function of patients with ankylosing spondylitis based on Keap1-Nrf2-ARE.Methods:120 cases of ankylosing spondylitis were selected as the studied objects and 60 healthy people from the medical center served as members of the normal control group.Pulmonary function parameters (FVC,FEV1,M VV,PEF,FEF25,FEF50,and FEF75) of the two groups were tested with German Automatic Pulmonary Function Test Instrument (Jager MasterScreen);ELISA was used to detect pathway protein in the serum of the two groups (Keap1,Nrf2),oxidative stress index (MDA,ROS,RNS,SOD,CAT,TAOC) and the content of cytokines (IL-18,TNF-α,IL-4,IL-35);the Westergren method was used to detect the erythrocyte sedimentation rate;the Hitachi 7060-type automatic biochemical analyzer was used to detect C-reactive protein and immunoglobulin. Results:Compared with the normal control group: ① FEV1,MVV,PEF,FEF50 and FEF75 of patients with ankylosing spondylitis decreased significantly (P < 0.01 or P < 0.05);compared with the Keap1 and Nrf2 normal group of ankylosing spondylitis,the FEV1,MVV,PEF,FEF50 and FEF75 of the Keap1 and Nrf2 abnormal group signiifcantly decreased (P<0.05 or P<0.01).②The Keap1,Nrf2,ROS,RNS,MDA in serum of patients with ankylosing spondylitis increased signiifcantly (P<0.01 or P<0.05),and the SOD,CAT,TAOC decreased signiifcantly (P<0.01 or P<0.05).③The IL-18,TNF- α,ESR and CRP in patients with ankylosing spondylitis signiifcantly increased (P<0.01),and the IL-4 and IL-35 decreased signiifcantly (P<0.01 or P<0.05).④ According to Spearman's analysis of correlation,FEV1,MVV,PEF,FEF50,FEF75 positively correlated with SOD,CAT,TAOC,IL-4 and IL-35,and negatively correlated with Keap1,Nrf2,ROS,RNS,MDA,IL-18,TNF- α, ESR,CRP,chest tightness,shortness of breath and dyspnea (P < 0.01 or P < 0.05).Conclusion:58.33%patients of ankylosing spondylitis had reduced lung function:their pulmonary function parameters such as FEV1,MVV,PEF,FEF50 and FEF75 significantly reduced;the above parameters of lung function positively correlated with antioxidant index and anti-inlfammatory cytokines;and negatively correlated with Keap1,Nrf2,the oxidation index,proinlfammatory cytokines,and inlfammation index.The expression of Keap1 and Nrf2 increased. After the activation of Keap1-Nrf2-ARE signaling pathway,antioxidation ability of the body decreased,which promoted the imbalance of cytokine and the increase of inlfammation index,and led to the increase of abnormal deposition of immune complex.The above could cause ankylosing spondylitis and damaged or destructed lung tissue,eventually reducing the lung function.