Mechanism Research Of Xinfeng Capsule On Improving The Cardiovascular Disease In Patients With Rheumatoid Arthritis Based On TLR4/NF-?B Pathway

1 Objective By using the method of retrospective analysis of clinical cases to explore risk factors combined cardiovascular damage in patients with rheumatoid arthritis;And based on TLR4/NF-?B signaling pathway research the traditional Chinese medicine(TCM)Xinfeng Capsule compound capsule on rheumatoid arthritis(RA)combined cardiovascular damage in patients with curative effect and mechanism of action.2 Methods2.1 Rheumatoid arthritis merger risk factor for cardiovascular damage analysis Collected in anhui province hospital rheumatism,2016.01.01-2016.05.31 hospital during the period of RA patients,all these patients general information collection(age,gender,duration,etc.);Clinical symptoms(joint tenderness and swelling and swelling index,etc.);Laboratory indicators(blood routine,biochemical full,autoantibodies,etc.);Check index(electrocardiogram,heart colour to exceed,etc.).In patients with RA general information,clinical symptoms,laboratory tests,and the heart colour to exceed to check information on the single factor analysis of combined with single factor as a result,the use of Logistic regression analysis RA multiple risk factors of CVD.2.2 Combined cardiovascular damage in patients with rheumatoid arthritis correlation analysis of clinical manifestation,laboratory indexes Sep 2016 to May 2016 in our hospital inpatient li rheumatism lead,randomly selected from 60 patients with RA with CVD,using american-made GE VIVID 7 heart ultrasonic diagnostic instrument testing RA with CVD group(60 cases)and normal control group(20 cases)NC,heart function.Test items include ejection fraction(EF%)and shortening fraction(FS%),right ventricular diameter value(RVOTD),aortic diameter(AODd)and so on heart function parameters.Application of flow cytometry(FCM)RA merger pathway in patients with CVD and NC peripheral blood index (TLR4,My D88,IRAK1,TRAF6,nf-kappa B)expression.Observation of RA with CVD patients with systemic symptoms and signs,cardiac symptoms integral,the integral quality of life,disease activity and DAS-28 integral value,etc.Using SPSS22.0software analysis the correlation between the index and heart function.2.3 Based on TLR4 / nf-kappa B signaling pathways,on patients with RA with CVD,XFC curative effect and mechanism of action I selected 60 patients with RA merger of CVD in hospital,were randomly divided into treatment group(air capsule)and control group(milt)to fluorine,30 cases each.Observed two groups of patients before and after treatment,quantitative values in the whole body joint symptoms,cardiac symptoms,life quality of integral value,DAS-28,differences of integral value;Using automatic biochemical analyzer test of two groups of laboratory index(RF,CRP,ESR and other inflammatory indicators);Choose ELISA to detect cytokine(TNF alpha,IL-1,IL-2,IL-6,IL-10);Choose Western blot detection signal path(TLR4,My D88,IRAK1,TRAF6,nf-kappa B)to improve the situation.3 Results3.1 Rheumatoid arthritis merger risk factor for cardiovascular damage analysis3.1.1 General situation2016.01.01-2016.05.31 between all the total of 392 cases of RA patients admitted to hospital,collect data based on 200 patients with complete data analysis.200 RA patients with male patients accounted for 24,176 female patients;Course 1 to 20 years,aged 22 to 83 years old,including a total of 78 cases of merger CVD,the total of39%.Cardiovascular disease includes heart valve disease by 58 cases,74.3% of CVD,ecg abnormal conduction 33 cases,42.3% of CVD,6 cases of coronary artery pathological changes,accounts for 7.6% of CVD,pericardial effusion in 1 case,1.2% of CVD.3.1.2 Merger CVD compared to unincorporated CVD patients with RA index Single factor analysis results show that RA merger CVD patients with RA unincorporated CVD,the two groups in age,duration,DAS28 score,RF,ESR,CRP,LDLC,TC,CCP,GLU,RVDd,LVDd,EF,FS on indicators such differences are significant(P<0.05).3.1.3 RA merger of CVD risk factors related to Logistic multivariate regression analysis In combination with single factor analysis results,there will be differences of indicators,to the Logistic multivariate regression method,the dependent variable into binary variables,namely the RA merger CVD patients,patients with RA unincorporated CVD,based on the principle of stepwise regression,using SPSS analysis,after adjustment for age,sex and RA course will be graded single factor analysis of DAS28,RF,ESR,CRP,TC,CCP,GLU into the equation for multiple regression analysis(into the standard 0.1,excluding standard is 0.1).Multi-factor analysis showed: the DAS28 score,RF,ESR,CRP,CCP and elevated levels of TC,RA patients will be increased the risk of CVD.EXP analysis results showed that the RF high positive rate of patients with CVD risk is nearly double the RF negative patients.B analysis results showed that the ESR and CRP inflammation index rose,RA with CVD risk increases nearly 20%.3.2 Combined cardiovascular damage in patients with rheumatoid arthritis correlation analysis of clinical manifestation,laboratory indexes3.2.1 RA and CVD and NC group cardiac function change detection results60 cases of RA with CVD patients and 20 cases than the rate of abnormal heart colour to exceed to the NC group,RA heart colour to exceed change detection results the abnormal rate was 86.7%,NC group abnormal rate of 35.0%.One group of patients with RA merger of CVD in the rate of abnormal heart colour to exceed,the highest is a decline in left ventricular diastolic function and main(21.7%),the abnormal rate of closed,then is simply left ventricular diastolic function decline,decreased left ventricular diastolic function and two main closed closed(15.0%)of the abnormal rate, followed by falling left ventricular diastolic function and two closed(13.3%)of the abnormal rate,etc.60 cases of RA with CVD patients and 20 cases of NC group heart colour to exceed total abnormal rate change detection results comparison,the difference was statistically significant(P < 0.05).3.2.2 RA and CVD group compared with NC group of cardiac function parameters Compared with NC group,RA combined CVD patients EF%,FS%,SV decreased significantly(P<0.01);RVOTD,AODd,LADd,LVDd significantly higher(P<0.01);The analysis of the two groups of RVDd indicators,there were no significant differences(P > 0.05).3.2.3 RA and CVD patients heart function parameters and DAS-28,joint symptoms integral analysis of the correlation RA and RVDd CVD patients heart function parameters and joint swelling were positively correlated(P<0.05);The rest of the cardiac function parameters,and partial joint symptoms integral,the statistical analysis was no significant difference(P > 0.05).3.2.4 RA and CVD patients heart function parameters and the correlation analysis of integral whole body symptoms and signs RA and CVD patients heart function parameters RVDd and languid negatively correlated(P<0.05);QRS and negatively correlated with loose stool pond(P<0.05);The rest of the cardiac function parameters,and the systemic symptom integral,the statistical analysis was no significant difference(P > 0.05).3.2.5 RA CVD patients heart function and cardiac symptoms integral parameters and correlation analysis RA and CVD patients heart function parameters of EF% and palpitation integral were positively correlated(P<0.05);PR,FS%,respectively,and dyspnea integral were positively correlated(P<0.05);The rest of the cardiac function parameters,and cardiac symptoms integral,the statistical analysis was no significant difference(P > 0.05). 3.2.6 RA and CVD patients heart function parameters and the correlation analysis of TLR4/NF-?B pathway RA and CVD patients heart function parameters of QRS was positively correlated with IRAK1;AODd and TLR4 were positively correlated;RVDd and negatively correlated with IRAK1,nf-kappa B;LVDd and IRAK1,nf-kappa B,TLR4 were positively correlated;FS% with IRAK1,nf-kappa B,TLR4 were positively correlated;SV with IRAK1,nf-kappa B,TLR4,TRAF6 were positively correlated;Correlation analysis are statistically significant(P < 0.05 or P < 0.01).3.3 Based on TLR4 / nf-kappa B signaling pathways,explore new wind capsule,in the treatment of RA with CVD patients,the clinical curative effect and mechanism of action3.3.1 Xinfeng Capsule clinical curative effect for the treatment of RA with CVD XFC group in the treatment of week 0,week 2,4 weeks of ACR20,ACR50,ACR70 respectively 0%/0%/0%,11.6%/5.0%/0%,26.6%/8.3%/3.3%;LEF group in the treatment of week 0,week 2,4 weeks of ACR20,ACR50,ACR70 respectively0%/0%/0%,8.3%/3.3%/0%,18.3%/5.0%/1.6%;indicating the difference between the two group ACR20,ACR50,ACR70 is not statistically significant(P >0.05).3.3.2 Two groups of cardiac function parameters before and after the treatment Before the treatment,two groups of RA with CVD patients,cardiac function parameters of no statistical significance(P > 0.05).XFC group after treatment,heart function parameter AODd,FS% have increased significantly(P < 0.05),and EF% show is lower(P < 0.05);LEF group of cardiac function parameters have no obvious difference(P >0.05).Compared with LEF group after treatment,XFC group after treatment FS%,degree of SV improved more significantly(P < 0.05).3.3.3 Two sets of quality of life scores were compared between before and after treatment Two groups of RA with CVD patients before treatment,its quality of life scores no statistical significance(P > 0.05).After treatment,two groups of quality of life always list shows significantly decreased(P < 0.01);In the two groups in the physical,psychological,social integration,and self-awareness ability score were significantly decreased(P < 0.01);The physiological function,social function integral,integral part of the indexes such as psychological function,XFC group improvement is more obvious in the LEF group(P < 0.05 or P < 0.01).3.3.4 The two groups before and after treatment HAQ,VAS and the change of the DAS-28 Before the treatment,two groups of RA with CVD patients health and DAS integral no significant difference(P > 0.05).After treatment,compared with before treatment,HAQ XFC group and LEF group after treatment,VAS,DAS-28 integral value lower(P <0.01),XFC group in improving HAQ level than LEF group(P < 0.01).3.3.5 Two groups of joints and systemic clinical symptom scores were compared between before and after treatment Before the treatment,two groups of RA with CVD patients integral joints and systemic clinical symptoms and signs have no obvious difference(P > 0.05).Two groups of patients after treatment,joint pain,swelling,tenderness,morning stiffness integral reduced significantly(P < 0.01),loss of appetite,languid integral,food after abdominal distention integral and systemic integral were reduced(P < 0.05 or P < 0.01),the clinical symptoms and signs were obviously improved;The joint pain and loss of appetite integral,less gas lazy words,languid integral,in XFC group has a better therapeutic effect in the LEF group(P < 0.05 or P < 0.01).3.3.6 Two sets of changes in laboratory indexes before and after treatment Before the treatment,two groups of RA with CVD patients,no statistical significance(P > 0.05).After treatment,the index values of RBC and HGB XFC group increased(P< 0.05 or P < 0.01),PLT,GLU,CK-MB,Ig G,Ig A,C3,C4 and ASO,RF,CRP,ESR, GPI,CCP-AB were significantly lower(P < 0.05 or P < 0.01);LEF group increased(P< 0.05),RBC ratio,ASO,PLT,GLU,Ig G RF,AGP,CRP,ESR,GPI,CCP-AB experiment index decreased(P < 0.05).Among them,GLU,CK-MB,RF,ESR,the CCP-AB laboratory indexes XFC group improvement is more obvious in the LEF group(P < 0.05 or P < 0.01).3.3.7 Cytokine changes before and after treatment in both groups Before the treatment,two groups of RA with cytokines in patients with CVD indicators no significant difference(P > 0.05).IL-10 XFC group was obviously increased(P <0.01),IL-1,IL-6,TNF-a significantly lower(P < 0.01);After treatment,LEF group of IL-10 factors also increased(P < 0.05),TNF-a cell also lower(P < 0.01).XFC group is LEF,on IL-6 cytokine inhibiting,more obvious(P < 0.05).3.3.8 Two groups before and after treatment of TLR4/NF-?B signaling pathway related protein expression changes Before the treatment,two groups of patients with RA pathways target protein expression has no obvious difference(P>0.05).Compared with before treatment,two groups of TLR4,My D88,IRAK1,TRAF6,nf-kappa B were significantly lower(P<0.01);Of XFC group is LEF in TLR4,TRAF6 and nf-kappa B protein expression level is more difference(P < 0.05 or P < 0.01).4 Conclusion4.1 Rheumatoid arthritis merger risk factor for cardiovascular damage analysis4.1.1Incidence of RA patients easily merge CVD,about 39%;RA and CVD is the main performance of heart valve disease,of CVD in 74.3%;4.1.2 Single factor analysis results show that the RA merger CVD risk happened with age,duration,DAS28 score,RF,ESR,CRP,LDLC,TC,CCP,GLU,RVDd,LVDd,EF,FS,Showed that in addition to traditional GLU,TC,LDLC and other cardiovascular risk factors,RA with CVD risk also happened with RF,ESR and CRP about inflammation index;4.1.3According to the results of multi-factor analysis DAS28 score,RF,ESR,CRP,CCP and elevated levels of TC,risk of CVD in patients with RA will rise;RF high positive rate of patients with combined CVD risk is nearly double the RF negative patients;The ESR and CRP inflammation index rose,RA with CVD risk increases nearly 20%.4.2 60 cases of RA and CVD patients clinical characteristics4.2.1 Selection of 60 patients with RA with CVD the cardiac function parameters abnormality rate is highest SV,RA patients with cardiac function parameters RVOTD,AODd,LADd,LVDd increased obviously,and the EF%,FS%,SV were significantly lower than normal;4.2.2 RA patients on cardiovascular disease,often hidden,it most often is in the heart colour to exceed,left ventricular diastolic function decline and closed,the second is simply left ventricular diastolic function decline,decreased left ventricular diastolic function and two main closed shut.4.3 The curative effect of Xinfeng Capsule in patients with RA and CVD and its effects on cardiac function4.3.1 Xinfeng Capsule can significantly improve the signs and symptoms of patients with RA and CVD integral,DAS-28 points and HAQ scores and the quality of life;4.3.2 Xinfeng Capsule can obviously improve rheumatoid arthritis patients' cardiac function parameters AODd,FS%,lower EF%,etc.,to improve the heart function;4.3.3 Xinfeng Capsule can improve the content of RBC,HGB,improve anemia,reduce RF,ESR,CCP-AB laboratory indexes such as,from a certain extent,delay the RA disease progression;4.3.4 Xinfeng Capsule for RA with CVD patients,by improving the suppression of inflammatory cytokines in serum IL-10,reduce proinflammatory factor,IL-6,IL-1TNF-a level,inhibit inflammation,relieve heart tissue immune injury.To fluorine,although in clinical efficacy rate,improve the symptoms of joints,and optimize the laboratory index,etc.,similar to the fresh air capsule role,but in its improve systemic symptoms and signs,optimizing the condition of heart function,regulating the expression of cytokines,etc,are not fresh air capsule effectively;And the treatment group,compared with control group,no significant adverse drug reactions.Fresh air capsule indicate that not only in improving cardiac function is better than that in control group,and its comprehensive effect is better than the control group.4.4 Based on TLR4/NF-?B signaling pathway to explore the mechanism of action of new wind capsule on the cardiac function of patients with RA4.4.1 RA and CVD patients heart function parameters and TLR4/NF-?B signaling pathway index of correlation analysis showed that the mechanism of action of new wind capsule on the cardiac function of patients with RA and TLR4/NF-?B signaling pathway has a certain relationship;4.4.2 Regulating pathway proteins: down TLR4,My D88,IRAK1,TRAF6,nf-kappa B protein expression,adjust the excessive activation of TLR4 / the nf-kappa B pathway,thereby reducing the downstream synthesis of inflammatory cytokines,reduce inflammation factor of body target organ damage;4.4.3 Regulating cytokine balance: cut IL-6,IL-1,TNF-a cell,increase IL-10,suppression of pro-inflammatory cytokines effect,anti-inflammatory effect,enhance reduce inflammatory mediators to joint symptoms and heart function damage.5 Summary This study shows that,the incidence of RA with CVD is as high as 40%,main show is heart valve disease,in addition to the traditional cardiovascular risk factors,such as blood glucose,blood lipid,RA patients with systemic inflammatory response and is associated with increased risk of CVD,RF high positive rate of patients with CVD risk is nearly double the RF negative patients,the ESR and CRP inflammation index rose,RA with CVD risk increases nearly 20%.Based on TLR4/NF-?B signaling pathway index correlation analysis showed that patients with RA with CVD Xinfeng capsule in the treatment of RA with CVD patients mechanism has relationship with the signal path: Xinfeng capsule can obviously improve joint symptoms in patients with RA with CVD,improve heart function,mainly through down TLR4,My D88,IRAK1,TRAF6,nf-kappa B protein expression,adjust the excessive activation of TLR4/NF-?B pathway,and then cut,IL-6,IL-1 TNF-a cell,increase IL-10,thus reducing inflammatory cytokines,reduce inflammation factors on the body of target organ damage.