| ObjectiveThis thesis is guided by traditional Chinese medicine(TCM)theory.It is based on the clinical observation.We are used the method of the large sample,randomized,double blind,parallel controlled and multi center clinical trial according to the principle of evidence-based medicine,and observe clinical symptoms,signs,laboratory indicators,the quality of life of patients of RA of the activity period of spleen-deficiency dampness type with Xinfeng Capsule(XFC) before and after treatment,and evaluate the effectiveness and safety of XFC,and contrasted with leflunomide(LEF).To the study of TCM in the treatment of RA In order to provide the experimental method of scientific and convincing results.To explore the pathogenesis of RA based on apoptosis rate and the expression of apoptosis related protein of Fas/FasL of CD4+T lymphocytes cells in peripheral blood of RA,and mechanisms of Xinfeng Capsule in the treatment of RA based on apoptosis rate and the expression of apoptosis related protein according to change after anf before treatment of XFC.Methods304 RA patients are from four research center(the first affiliated hospital of Anhui traditional Chinese medicine university,the first affiliated hospital of medical university of Anhui,the affiliated hospital of Bengbu medical college,the affiliated YiLiShan hospital of WanNan medical college)from 2013 July to 2014 May,divided into the treatment group and the control group at random.Taking XFC(3 capsules per time,tid)+LEF(simulated agent) in the treatment group,and LEF(10mg per time,QN)+XFC(simulated agent) in the control group.Excluding 22 cases that do not meet the inclusion and exclusion criteria and failed to complete the test in patients,282 patients have completed clinical trials in accordance with the requirements.The date of starting and observation of treatment of all patients were date to obtain the random number.Every course is 4 weeks.Each patient is observed for 3 courses, and visited 1 times 4 weeks after treatment.Patients with RA were recorded clinical symptoms,signs,laboratory indicators, quality of life,mental status,concomitant medications,and adverse events in treatment processes(the fourth week,the eighth week) and after treatment(the twelfth week).Experiment obiect is to select 28 patients with RA from the department of rheumatism of the first affiliated hospital of Anhui university of TCM.Normal control group(NC) is to select 10 healthy persons.The apoptosis levels of Annexin V of CD4+T lymphocytes in patients with RA and control individuals are measured by flow cytometry.The expression levels of fas,fasL,caspase8,caspase3,bcl-2 and bax mRNA are measured by qRT-PCR and fas,fasL,caspase8,caspase3 by WB.To analyze the correlation between apoptosis rate, expression of apoptosis proteins and clinical activity parameters, In order to explore the mechanisms of XFC in the treatment of RA. Result Results of clinical studiesThe overall effect of the two groups after treatment:Compared ACR20,ACR50,ACR70 between XFC group and LEF group in the 4,8,12,16 week after treatment.The results showed that had not significant difference XFC group and LEF group(P>0.05).The overall effect is quite of the XFC group and LEF group.DAS28-3 score decreased significantly of XFC group and LEF group after treatment(P<0.01).The results showed that had not significant difference between XFC group and LEF group after treatment,The overall effect is quite of the XFC group and LEF group.Laboratory indexes:ESR,CRP,RF,CCP,GPI in two groups before and after treatment:In XFC group,numerical value of ESR,CRP,RF is lower after than before treatment.P>0.05,There is not statistics difference.CCP is reduced significantly.P < 0.01,There is significant difference.There are not statistics difference in comparison of ESR,CRP,RF,CCP,GPI between XFC group and LEF group after treatment.P>0.05.Comparison of platelet parameters in two groups before and after treatment: In LEF group,numerical value of PLT is lower after than before treatment.There is statistics difference.P<0.05,numerical value of PCT is higher after than before treatment.There is statistics difference.P<0.05.There are not statistics difference in comparison of PLT,PCT, PDW,MPV between XFC group and LEF group after treatment.P>0.05.IgA,IgG,IgM in two groups before and after treatment: In XFC group,comparison of IgA,IgG before and after treatment.There are no statistics difference.P > 0.05.There are no statistics difference in comparison of IgA,IgG after treatment,and difference after and before treatment between XFC group and LEF group.P>0.05.There is no statistics difference in comparison of IgM difference after and before treatment between XFC group and LEF group.P>0.05.Comparison of coagulation index in two groups before and after treatment: In XFC group,Numerical value of TT is lower after than before treatment.There is statistics difference.P<0.05.In XFC group,Numerical value of D-D is much lower after than before treatment.There is significant difference.P < 0.01.In LEF group,There is statistics difference in comparison of D-D before and after treatment.P<0.05. TCM symptomsThe results showed that total scores of symptoms of TCM is significantly decrease.Comparison of value before and after treatment in XFC or LEF group,There is significant difference.P<0.01.There are statistics difference in comparison of value of symptoms of TCM after treatment, and difference after and before treatment between XFC group and LEF group.P<0.05. Curative effect of XFC group is better than that of LEF group.All scores of the main symptoms of TCM(joint pain,night pain worse,the degree of joint swelling,fatigue,food intake)is significantly decreased.Comparison of value before treatment and after treatment in XFC or LEF group,There is significant difference.P<0.01. There is significant difference in comparison of value of fatigue or food intake after treatment between XFC group and LEF group.P<0.01.Curative effect of XFC group is better than that of LEF group.All scores of the secondary symptoms of TCM(adverse joint flexion degree,morning stiffness,the degree of joint tenderness,loose stool) is significantly decreased.Comparison of value before and after treatment in XFC or LEF group, There is significant difference.P<0.01.There is significant difference in comparison of value of loose stool after treatment between XFC group and LEF group.P<0.01.Curative effect of XFC group is better than that of LEF group.All scores of assessment of patients to joint pain,the overall and assessment of physician to the overall are significantly decreased.Comparison of value before and in the 4,8,12 week after treatment in XFC or LEF group,There is significant difference.P groups.There are statistics difference.P<0.05.Curative effect of XFC group is better than that of LEF group.Numerical value of HAQ 、 RFQOL 、 SDS 、 SAS of patients are significantly decreased. Comparison of Numerical value before and after treatment in XFC or LEF group,There is significant difference.P<0.01.There is statistics difference in comparison of SDS difference after treatment minus before treatment between XFC group and LEF group.P<0.05.Comparison of joint X-ray grading in XFC or LEF group before and after treatment,P>0.05.and after treatment between XFC group and LEF group.P>0.05.There is not statistics difference.There are not statistics difference in comparison of the incidence of adverse events,liver function,renal function,routine blood test,urine routine,stool routine, electrocardiographic pattern between XFC and LEF groups.P>0.05. The results of the experimentalThere is significant difference in comparison of the apoptosis levels of CD4+T lymphocytes between XFC group and NC group,or between LEF group and NC group before treatment.P<0.001. There is significant difference in comparison of cells apoptosis levels after and before treatment between XFC group and LEF group.P<0.001. There is not statistics difference between XFC group and LEF group after treatment.There is significant difference in comparison of the expression levels of fas,fasL,caspase8,caspase3,bcl-2 and bax mRNA between XFC group and NC group,or between LEF group and NC group before treatment.P<0.001.There is statistics difference in comparison of expression levels after and before treatment between XFC group and LEF group.P<0.001.There is significant difference in comparison of expression of the apoptosis gene bcl-2 mRNA between XFC group and LEF group after treatment.P<0.001.There is significant difference in comparison of the expression of Fas,FasL,caspase3 between XFC group and NC group before treatment.P < 0.001.and the expression of caspase8.There is statistics difference.P<0.05.There are significant difference in comparison of the expression of Fas,FasL,Caspase8 and Caspase3 after and before treatment in XFC group.P<0.001.and the expression of Fas,Caspase8 and Caspase3 after and before treatment in LEF group.There are statistics difference.P<0.001.In LEF group,There is statistics difference in comparison of expression of FasL after and before treatment.P<0.05.There are not statistics difference in comparison of expression of Fas,FasL,Caspase8 and Caspase3 between XFC group and LEF group after treatment.P>0.05.The correlation between the expression of apoptosis signaling proteins and clinical activity parameters were analyzed:The apoptosis levels of CD4+T lymphocytes in patients with RA is negatively related with ESR,RF.Fas is negatively related with ESR,CRP.Caspase3 is negatively related with ESR.Bcl-2 is positively correlated with ESR.Bax is negatively related significantly with the number of swollen joints.The results showed that XFC,LEF are effective in treatment of RA.XFC can decrease the number of tender,swollen of joint and improve symptoms of TCM,fatigue,reduce food intake,loose stool.Combined adverse events is quite between XFC group and LEF group.XFC can increase the level of apoptosis of CD4+T cells in patients with RA,Up-regulated the expression of apoptosis protein fas,fasL, bax, caspase8 and caspase3,and down-regulation the expression of apoptosis protein bcl-2.Expression of some apoptosis proteins are closely related with indexes of the main clinical observation. ConclusionsThe curative effect of XFC in the treatment of RA is equivalent to LEF.Clinical effect of XFC is good.XFC can relieve significantly the clinical symptoms and signs,reduce laboratory indicators and improve quality of life in patients with RA.XFC can reduce significantly the number of joint tenderness and swelling,and improve the TCM symptoms integral,fatigue,food intake,loose stool,SDS integral.Not only XFC can treat RA,but also has the overall adjustment, improve patient symptoms,improve resistance of patients,alleviate the pressure of patients,and improve mental state of patients.The incidence of adverse events is equivalent to XFC group and LEF group.The majority of them is light,moderate degree of adverse reactions.That have not affected the treatment.XFC can increase level of apoptosis of CD4+T lymphocytes cells in patients with RA,up-regulated the expression quantity of apoptosis gene relatet protein fas,fasL, bax, caspase8 and caspase3,and down-regulation the expression quantity of apoptosis gene relatet protein bcl-2.The expression level of some apoptosis proteins is closely related with ESR,RF and the number of swollen joints of the main clinical observation indexes.It is speculated that the mechanism of treatment RA of XFC probably regulate Fas/Fas L apoptosis pathway,regulate the expression quantity of apoptosis related proteins,up-regulate the expression quantity of urge apoptosis protein,down-regulate the expression quantity of apoptosis suppressor protein,promote cell apoptosis,and can prevent the progression of the RA disease.XFC is beneficial to the prevention and treatment of RA.In short,XFC is good herb in the treatment of RA.It is worth further mining. |
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