Based On MyD88-dependent Signaling Pathway,the Mechanism Of Treatment Of Rheumatoid Arthritis By Professor Ding E,Yiqi Yangxue Tongluo Method

1.Objective To observe the therapeutic effect of Professor Ding Wei,Yiqi Yangxue Tongluo combined with tripterygium glycosides on rheumatoid arthritis(RA),and MyD88-dependent signaling pathway,pro-inflammatory/inflammatory cytokines and experiments Changes in room indicators.To elucidate the correlation between MyD88-dependent signaling pathway and RA,and to study the effect of Yiqi Yangxue Tongluo combined with tripterygium glycosides on MyD88-dependent signaling pathway in RA patients and to explore its mechanism.2.Methods 2.1 Theoretical research Through a large number of literature searches and researches,this paper explores the relationship between RA and TCM blood deficiency and blood stasis,analyzes and elucidates the pathogenesis and internal relationship of RA Chinese medicine,and expounds the theoretical basis of Yiqi Yangxue Tongluo therapy for RA.2.2 Clinical research 40 patients with early-stage RA who were admitted to the rheumatology department of Anhui Provincial Hospital of Traditional Chinese Medicine from 2017.9 to 2018.5.They were randomly divided into 2 groups,20 cases in each group(Yiqi Yangxue Tongluo Recipe + Tripterygium wilfordii glycosides)and the control group(Tracium sinensis glycosides),and 20 normal physical examination personnel were selected from the physical examination center of the hospital.Normal control group.IL-1?,IL-10 and TNF-? were detected by enzyme-linked immunosorbent assay(ELISA);TLR4,MyD88,TAK1,IKK,NF-KBp65 were detected by real-time PCR;hs-CRP,RF,and CCP,Ig G,Ig A,Ig M,C3,C4,liver function,renal function,etc.;automatic ESR analyzer to detect ESR;automatic blood and urine analyzer to detect blood routine,urine routine,ECG machine to detect ECG.Calculate DAS28,VAS score,and TCM syndrome score.The quality of life,HAQ,SAS,and SDS were evaluated by questionnaire scale.3.Results 3.1 Theoretical Results 3.1.1 The MyD88-dependent signaling pathway plays an important role in the pathogenesis of RA.3.1.2 MyD88-dependent signaling pathway regulates the release of inflammatory factors and affects the immune inflammation of RA.3.1.3 Traditional Chinese medicine qi and blood deficiency is the cause of RA,and participates in the pathological evolution of RA.3.1.4 Yiqi Yangxue Tongluo Method is an effective treatment for RA.3.2 Clinical research results 3.2.1 Changes and correlation of serum indexes in patients with RA The levels of TLR4,MyD88,TAK1,IKK,NF-KBp65,TNF-? and IL-1? in RA group were higher than those in normal group(P<0.05 or P<0.01),and IL-10 was lower than normal group(P<0.01),and CCP,ESR,CRP,and RF in RA group were significantly higher than normal group(P<0.01);TLR4 was positively correlated with CRP in RA group(P<0.05),and MyD88 was positively correlated with CCP and DAS28(P<0.05 or P<0.01),TAK1 was positively correlated with RF(P<0.05),NF-KBp65 was positively correlated with CCP(P<0.05),IKK had no significant correlation with disease activity index;TNF-? and CCP and CRP were positively correlated(P<0.05),IL-1? was negatively correlated with RF(P<0.05),positively correlated with DAS28(P<0.05),IL-10 was negatively correlated with ESR and DAS28(P<0.05)..TLR4 was negatively correlated with IL-10(P<0.05),MyD88 was positively correlated with TNF-?,TAK1 was positively correlated with IL-1?(P<0.05),and NF-KBp65 was positively correlated with IL-1?(P<0.05).P<0.05),there was no correlation between IKK and TNF-?,IL-1? and IL-10(P>0.05).RA group TLR 4 was associated with joint swelling,anorexia,female menstrual flow,dark color,blood clot,and menstrual delay(P<0.05);MyD88 increased after exertion,pale or sallow,pale menstruation,color Dark,blood clots,menstrual delay,dull tongue,and ecchymosis were positively correlated(P<0.05 or P<0.01);TAK1 and joint swelling,shortness of breath,anorexia,spontaneous sweating,less menstrual flow,darker color,There was a positive correlation between blood clots and menstrual period(P<0.05 or P<0.01);IKK was positively correlated with joint pain,morning stiffness,shortness of breath,and weak pulse(P<0.05);NF-KBp65 was tender with joint pain,pale complexion or There was a positive correlation between chlorosis(P<0.05).TNF-? was associated with swelling of the joints,morning stiffness,aggravation after exertion,anorexia,dull tongue,and ecchymosis(P<0.05);IL-1? and joint pain,shortness of breath,pale complexion or chlorosis,and low menstrual flow in women Dark color,blood clot,and menstrual delay were positively correlated(P<0.05);IL-10 was negatively correlated with joint tenderness and spontaneous sweating(P<0.05).TLR4 was positively correlated with HAQ in RA patients(P<0.05 or P<0.01);MyD88 was positively correlated with SAS and SDS(P<0.05 or P<0.01);TAK1 was positively correlated with quality of life;IKK and SAS,SDS was positively correlated(P<0.05 or P<0.01);NF-KBp65 was positively correlated with SDS(P<0.05).3.2.2 Clinical efficacy of Yiqi Yangxue Tongluo combined with tripterygium glycosides in the treatment of RA There was no significant difference in the total effective rate between the study group and the control group before and after treatment(P>0.05).However,the effective rate of treatment in the study group was significantly higher than that in the control group(P<0.01).3.2.3 Effect of Yiqi Yangxue Tongluo Method Combined with Tripterygium Glycosides on the Level of MyD88-dependent Signaling Pathway in RA Patients There were no significant differences in the values of TLR4,MyD88,TAK1,IKK and NF-KBp65 between the two groups(P>0.05).After treatment,the TLR4,MyD88,and NF-KBp65 in the study group were significantly lower(P<0.05),and the control group was significantly lower in MyD88 and IKK(P<0.05).After treatment,the two groups of MyD88 were compared.There was no significant difference(P>0.05).The study group had an advantage in reducing TLR4 and NF-KBp65(P<0.05).3.2.4 Effect of Yiqi Yangxue Tongluo Method Combined with Tripterygium Glycosides on the Levels of TNF-?,IL-1? and IL-10 in Patients with RA There were no significant differences in the levels of TNF-?,IL-1? and IL-10 between the two groups(P>0.05).After treatment,TNF-? and IL-1? were significantly decreased in the study group(P<0.01),IL-10 was significantly increased(P<0.01),IL-1? was effectively decreased in the control group(P<0.01),and IL-10 was also observed.Elevated(P <0.01).Compared with the two groups,IL-1? and IL-10 were decreased in both groups,but the study group did not predominate in reducing IL-1? level(P>0.05),and the study group reduced TNF-? and liter.The level of high IL-10 was significantly better than that of the control group(P<0.05 or P<0.01).3.2.5 Effect of Yiqi Yangxue Tongluo Method Combined with Tripterygium Glycosides on Laboratory Index of RA Patients There were no significant differences in the indexes between the two groups before treatment(P>0.05).After treatment,the CCP,ESR,CRP,RF,Ig G,Ig A,C3,and C4 values of the study group were decreased(P<0.01 or P<0.05),and the ESR,CRP,Ig G,C3,and C4 of the control group were also decreased(P< 0.01 or P < 0.05).Compared with the two groups after treatment,the study group was more effective in improving CCP,ESR,CRP,RF,Ig A(P<0.05).3.2.6 Effect of Yiqi Yangxue Tongluo Method Combined with Tripterygium Glycosides on TCM Syndrome Score of RA Patients There was no significant difference in TCM syndrome scores between the two groups before treatment(P>0.05).After treatment,the two groups played a role in improving joint swelling,pain,morning stiffness,and fatigue after exertion(P<0.01 or P<0.05).The study group improved joint swelling,morning stiffness,shortness of breath,fatigue,and fatigue.Anorexia,pale or sallow,spontaneous sweating,low menstrual flow,dark color,blood clots,delayed menstruation,dull tongue,and ecchymoses were better than the control group(P<0.01 or P<0.05).In the improvement of patients with qi and blood deficiency and blood stasis syndrome,shortness of breath,fatigue,fatigue,anorexia,pale or sallow,spontaneous sweating,less menstrual flow,darker color,blood clots,menstrual delay,dull tongue There was significant effect on ecchymoses(P<0.05 or P<0.01).3.2.7 Effect of Yiqi Yangxue Tongluo Method Combined with Tripterygium Glycosides on Levels of DAS-28 and VAS in Patients with RA There was no significant difference between DAS-28 and VAS in the two groups before treatment(P>0.05).After treatment,both groups of DAS-28 and VAS were significantly lower(P<0.05 or P<0.01);the study group was more significant than the control group(P<0.05).3.2.8 Effect of Yiqi Yangxue Tongluo Method Combined with Tripterygium Glycosides on Quality of Life Related Indexes in Patients with RA There were no significant differences in the quality of life related indicators between the two groups before treatment(P>0.05).After treatment,the HAQ,SAS and SDS of the two groups were decreased(P<0.05 or P<0.01).Among them,the study group was more effective than the control group in reducing HAQ,SAS and SDS(P<0.05 or P<0.01).4.Conclusion 4.1 Changes of MyD88-dependent signaling pathways,inflammatory factors and their correlation in RA patients The levels of TLR4,MyD88,TAK1,IKK,NF-KBp65,TNF-alpha and IL-1beta in RA patients were higher than those in normal subjects,athe levels of IL-10 were lower than those in normal subjects.MyD88-dependent signaling pathway is closely related to disease activity,and MyD88-dependent signaling pathway is positively correlated with inflammatory factors TNF-alpha,IL-1bet,negatively correlated with IL-10.Meanwhile,pathway indicators and inflammatory factors are closely related to quality of life,health status,quality of life,anxiety and depression,deficiency of Qi and blood and stagnation of collaterals in traditional Chinese medicine.4.2 Clinical Observation of Yiqi Yangxue Tongluo Method Combined with Tripterygium Glycosides on Patients with RA and Its Influence on Various Indicators Yiqi Yangxue Tongluo Method combined with Tripterygium wilfordii polysaccharide tablets has significant curative effect on RA,which can effectively control the disease,reduce disease activity,improve the symptoms of qi and blood deficiency,blood stasis and obstruction,relieve joint function and symptoms,reduce anxiety and depression.Status to improve the health and quality of life of patients.Yiqi Yangxue Tongluo method combined with tripterygium glycosides can effectively prevent the gastrointestinal reaction of tripterygium wilfordii tablets and improve the inhibition of female gonads.Yiqi Yangxue Tongluo combined with tripterygium glycosides can effectively reduce the levels of TLR4,NF-KBp65 and TNF-? in RA patients,increase IL-10 levels,and reduce the levels of CCP,ESR,CRP,RF and Ig A in RA patients.4.3 Possible Mechanism of Yiqi Yangxue Tongluo Method Combined with Tripterygium Glycosides in Treating RA 4.3.1 Yiqi Yangxue Tongluo method combined with tripterygium glycosides can down-regulate the expression of TLR4 and NF-KBp65 to inhibit the over-activation of MyD88-dependent signaling pathway,thereby inhibiting the release of downstream inflammatory factors and reducing the inflammatory response.4.3.2 Yiqi Yangxue Tongluo Method combined with Tripterygium wilfordii glycosides can reduce the immune inflammation by down-regulating TNF-?,up-regulating IL-10,inhibiting the pro-inflammatory response and increasing the anti-inflammatory response.