Mechanism Research Of Xinfeng Capsule On Improving Cardiopulmonary Function In Patients With Ankylosing Spondylitis Based On The Signal Path Of NF-κB-iNOS-NO

1ObjectiveObservation of cardiopulmonary function in AS patients and the effect of Xinfengcapsule(XFC) on Ankylosing Spondylitis(AS),and make investigation in themechanism of the effect of XFC onAS.2Methods2.1Theoretical studyThrough the study of a large number of literature, the relationship between spleendeficient and cardiopulmonary disease of ankylosing spondylitis is analyzed.The TCMetiology and pathogenesis of cardiopulmonary disease of ankylosing spondylitis issummed up,and the TCM theory basis about treatment of cardiopulmonary disease ofankylosing spondylitis from the spleen is interpreted.2.2Clinical study120patients with AS according to random number table is divided into researchgroup (Xinfeng capsule+traditional Chinese medicine fumigation+treatment basedon syndrome differentiation of traditional Chinese medicine),60cases in control group(Sulfa-salazine+traditional Chinese medicine fumigation+treatment based onsyndrome differentiation of traditional Chinese medicine).The cardiac function is detected by GE VIVID7ultrasonic diagnostic instrument.The lung function is measured by Jager MasterScreen MIR Spirolab. reactive oxygenspecies(ROS), reactive nitrogen species(RNS), malondialdehyde(MDA),superoxidedlismutase(SOD), catalase(CAT), total antioxidative capacity(TAOC), Nuclearfacter-KappaBp65(NF-κB p65), iNOS, NO, interleukin-1β(IL-1β), IL-4, IL-10,TNF-αare detected by using ELISA kits. The level of BAnd T Lymphocyte Attenuator(BTLA)is measured by using flow cytometry. The relevant laboratory indexes aredetected,such as immunoglobulin G(IgG), IgA, IgM, complement component3(C3),C4,erythrocyte sedimentation rate(ESR),cross-reacting protein(CRP).The integral values of the following indicators is calculated:visual analog scale(VAS),Bathankylosing spondylitis disease active index(BASDAI), Bath ankylosing spondylitisfunctional index(BASFI),Bath ankylosing spondylitis global index(BAS-G),physicalfunctioning(PF),social functioning(SF),role limitation due to physical problems(RP),role limitation due to emotional problems(RE),body pain(BP),mental health(MH),vitality(VT),general health(GH),self-rating anxiety scale(SAS),self-rating depressionscale(SDS).The relationship between cardiopulmonary function and the above indexesis analyzed by using statistical software SPSS17.0.Compared the curativeeffect,cardiopulmonary function variation,symptoms and signs, the quality of life andother related indicators about before and after the treatment of two groups.3The results3.1Theoretical study results3.1.1Cardiopulmonary disease is common in patients withASCardiopulmonary disease is common in patients with AS. The clinicians should paygreat attention to theAS the occurrence of cardiopulmonary lesions.3.1.2Spleen deficient through cardiopulmonary disease process ofASCardiopulmonary disease of ankylosing spondylitis is associated with spleendeficiency.The spleen-qi deficiency in early temper leads to the less nourishment of theheart and lung.Dysfunction of the spleen in transport in late temper leads to theabnormal of the water such as phlegm turbid,blood stasis which are stranded on theheart and lung.Therefore,spleen deficient will be of great importance incardiopulmonary disease process of ankylosing spondylitis.3.1.3Spleen deficient is the main pathogenesis of cardiopulmonary disease process ofASSpleen deficient is the basis of cardiopulmonary disease process of ankylosingspondylitis. Weakness of the spleen and the stomach,disharmony between ying andwei,less nourishment of the heart and lung.Weakness of the spleen and the stomach,dampness originating from interior,the heart and lung are affected.Weakness of the spleen and the stomach, phlegm and blood stasis alternating knot, the heart and lungare blockage.3.2Clinical study results3.2.1The change of cardiopulmonary function in patients withAS in this studyThe change of cardiac function in patients with AS in this study:The abnormalresults of cardiac function is47(39.17%) in120AS by using GE VIVID7ultrasonicdiagnostic instrument.Compared with the normal group, the AS patients peak E, E/Aratio, ejection fraction rate (EF%) are significantly decreased,A peak increasesignificantly.The change of lung function in patients with AS in this study:The abnormalresults of lung function is69(57.50%) in120AS by using Jager MasterScreen MIRSpirolab.Compared with the normal group, theAS patients FEV1,MVV,PEF,FEF50,FEF75are significantly decreased.3.2.2The change of BTLAand cytokines in patients withAS in this studyCompared with the normal group, theAS patients BTLA/CD3+T,BTLA/CD4+T,IL-4,IL-10are significantly decreased,IL-1β,TNF-α increase significantly.3.2.3The change of Oxidative stress path index and basic index in patients with ASin this studyCompared with the normal group, the AS patients SOD,CAT,TAOC are decreased,ROS,RNS,MDA,NF-κB p65,iNOS,NO increase significantly.3.2.4Correlation research of cardiopulmonary function in patients with ankylosingspondylitisCorrelation analysis show, AS patients with cardiac function parameters E, E/A,EF%are negatively correlated with duration, VAS,BASDAI.AS patients with cardiac function parameters E is positively associated withpalpitation. E, E/A are negatively correlated with less gas lazy words. EF%isnegatively correlated with palpitation, less gas lazy words, languid, abdominaldistension after food. AS patients with cardiac function parameters E/A, EF%is positively associatedwith GH. A is negatively correlated with VT,MH.E/A is positively associated withRE.E, E/Aare negatively correlated with SAS,SDS.AS patients with cardiac function parameters E is positively associated withIL-4,IL-10while negatively correlated with TNF-α,ESR,CRP,IgG. E/A is positivelyassociated with BTLA/CD3+T,BTLA/CD4+T while negatively correlated with IL-1β,TNF-α,CRP. EF%is positively associated with BTLA/CD4+T while negativelycorrelated with C3. FS%is positively associated with IL-10.AS patients with cardiac function parameters E is negatively correlated withNF-κB p65,iNOS,NO,ROS,RNS,MDA while positively associated with SOD,CAT,TAOC. A is positively associated with NF-κB p65. E/A is negatively correlated withNF-κB p65,iNOS,NO.EF%is negatively correlated with NO.FS%is negativelycorrelated with iNOS,NO.AS patients with lung function parameters FEV1,MVV,PEF,FEF75are negativelycorrelated with duration. FVC is negatively correlated with VAS,BASDAI.FEV1,MVVis negatively correlated with BASDAI.AS patients with lung function parameters FVC is positively associated withRE,VT while negatively correlated with palpitation, abdominal distension after food.FEV1,MVV are positively associated with GH,VT while negatively correlated withchest tightness. FEV1,MVV,FEF50, FEF75are negatively correlated with dyspnea, lessgas lazy words, languid. FEF75is negatively correlated with SAS,SDS.AS patients with lung function parameters FEV1is negatively correlated withESR,IgG.MVV is negatively correlated with ESR,IgM.FEF75is negatively correlatedwith C3,IgM. FVC is positively associated with IL-4,IL-10while negatively correlatedwith IL-1β,TNF-α.FEV1,PEF are positively associated withBTLA/CD3+T,BTLA/CD4+T, IL-4while negatively correlated with IL-1β.FEV1is negatively correlated withTNF-α.MVV is positively associated with BTLA/CD4+T while negatively correlatedwith TNF-α.FEF75is positively associated with BTLA/CD4+T. AS patients with lung function parameters FEV1,FEF50are negatively correlatedwith ROS,RNS,MDA while positively associated with SOD,CAT,TAOC.MVV isnegatively correlated with ROS,MDA while positively associated with SOD,TAOC.PEF is negatively correlated with ROS while positively associated with SOD,CAT.FEF75is negatively correlated with ROS, RNS while positively associated withSOD.FEV1,MVV,PEF,FEF50,FEF75are negatively correlated with NF-κBp65,iNOS,NO.3.2.5Correlation research of NF-κB p65-iNOS-NO in patients with ankylosingspondylitisNF-κB p65of AS patients is positively associated with ROS,RNS,MDA,TNF-α,ESR while negatively correlated with SOD,TAOC,IL-4,IL-10,BTLA/CD3+T,BTLA/CD4+T.iNOS is positively associated with ROS,RNS,MDA,TNF-α,Hs-CRP,BTLA/CD3+T while negatively correlated with SOD,TAOC.NO is positivelyassociated with ROS,MDA,IL-1β,ESR,Hs-CRP while negatively correlated with SOD,TAOC,BTLA/CD4+T.3.2.6XFC has the following function in patients withAS.The clinical curative effect of XFC is better than control group.The TCM totaleffective rate is no significant difference with control group while the efficiency issignificantly higher than control group.XFC can obviously increase the cardiac function parameters E,E/A,EF%whilesignificantly reduce A. The cardiac function is improved.XFC can obviously increase the lung function parameters FEV1,MVV, PEF,FEF25,FEF50,FEF75. The lung function is improved.XFC can obviously improve the patient’s clinical symptoms, such as back pain,sacroiliac joint tenderness, lumbar spinal activities limited integral, palpitations, chestcongestion, shortness of breath, less gas lazy words.XFC can significantly reduce the scores of VAS,BASDAI,BASFI,BAS-G.Thepathogenic condition is improved. XFC can significantly reduce the scores of SAS,SDS while obviously increasethe all dimensions integral of quality of life.XFC can significantly reduce the expression of NF-κB p65,iNOS, NO.XFC can obviously increase SOD,TAOC while significantly reduce ROS,RNS,MDA.XFC can obviously increaseBTLA/CD3+T, BTLA/CD4+T,IL-4,IL-10whilesignificantly reduce IL-1β,TNF-α.XFC can significantly reduce ESR, hs-CRP while obviously increase C3.4Conclusion4.1Cardiopulmonary function is impaired in patients withAS.4.2Spleen deficient has important consequences for cardiopulmonary disease processofAS.4.3Cardiopulmonary diseases exist in the AS patients, characterized by lower cardiacand pulmonary function parameters. The level of cardiopulmonary function parameteris closely related to NF-κB p65,iNOS,NO,ROS,RNS,MDA,SOD,TAOC,BTLA/CD3+T,BTLA/CD4+T,IL-4,IL-10,IL-1β,TNF-α,ESR,CRP,VAS,BASDAI,BASFI,BAS-G,SAS,SDS, quality of life.These indicate that oxidative stress, immune inflammatoryreactions involved in the process of cardiopulmonary diseases.The more obvious thecardiopulmonary function reduces, lower quality of life and higher anxiety depressionmood.4.4The curative effect of XFC group is significantly better than SASP group, asreflected in improving cardiopulmonary function, reducing the acute phase reactant,increasing BTLA expression, balancing the cytokines, controling clinical symptomsand signs, improving anxiety and depression, improving quality of life.4.5The mechanism that XFC improves cardiopulmonary function of AS patients maybe: inhibiting the NF-κB-iNOS-NO signaling pathway activation; reducing oxidationindex, inflammatory cytokines and inflammatory index level; raising BTLA expressionfrequency, anti-oxidation index; suppressing inflammatory cytokine levels; enhancing the antioxidant capacity, correcting cytokine imbalance, reducing inflammation andabnormal immune complex deposition, reducing the damage that inflammation affectscardiopulmonary viscera.In the end, the cardiopulmonary function is improved.