The Observation Of 5-year Radiology In The Treatment Of Rheumatoid Arthritis By Heat Clearing And Activating Blood Recipe And The Effect Of Its Decomposed Formulas On TNF-α And IL-6

Rheumatoid arthritis(RA)is an autoimmune disease characterized by symmetrical polyarthritis as the main clinical manifestation.It is characterized by chronic inflammation of joint synovium and progressive joint destruction.The morbidity rate of rheumatoid arthritis in 5 to 10 years is as high as 60%.More than half of patients with a 10-year disease duration cannot work.It is one of the major disabling diseases in the world and has a huge impact on society,families and individuals.In the 2012 ACR definition of poor prognosis of RA,bone erosion of joint imaging was listed as the main indicator.According to Triditional Chinese medicine(TCM),the disease belongs to:multiple arthralgia,severe and migratory arthralgia.The further development of the disease can injury bones and cause bone erosion.In recent years,domestic and foreign efforts have been devoted to delaying the progress of bone destruction in rheumatoid arthritis.There are more and more studies on prevention and treatment of bone destruction by Chinese medicine,and Chinese medicine has become an important way to prevent rheumatoid arthritis bone destruction.Modern studies suggest that inflammatory cytokines such as TNF-α and IL-6 are involved in the process of bone erosion in rheumatoid arthritis,and inflammation is an important cause of local and systemic bone loss in patients with rheumatoid arthritis.As soon as possible to inhibit the production of inflammatory cytokines,can effectively prevent or slow the joint synovial and cartilage lesions.Our department according to active period of pathogenesis of RA characteristics combined with years of clinical experience,emphasis on moist heat and phlegm are the key pathogenesis of active RA and the pathological key of bone destruction,Qingrehuoxue therapy is the basic treatment of active RA.We have a randomized multi-center cohort study on active RA with Heat Clearing and Activating Blood Recipe from 2007 to 2009,which shows this decoction is good at relieving joint swelling and pain,decreasing CRP&ESR and protecting patients’ joint function.The radiological evaluation and long-term efficacy evaluation of RA patients treated withHeat Clearing and Activating Blood Recipe for 1-3 years showed that the Recipe can delay the rate of bone destruction in patients with long-term.Based on the above research basis,this study will further evaluates the long-term efficacy of Heat Clearing and Activating Blood Recipe in the treatment of RA to delay bone destruction for a 5-year period from the perspective of radiology.And based on the principles of heat-clearing,damp-heating and blood-activating,the preliminary experimental study was conducted on the Heat Clearing and Activating Blood Recipe.The effect of Heat Clearing and Activating Blood Recipe on the inflammatory cytokines TNF-a and IL-6 in serum of CIA rats was observed.To investigate the possible mechanism of Heat Clearing and Activating Blood Recipe in delaying bone destruction,and further clarify the role of Heat Clearing and Activating Blood Recipe in the treatment of rheumatoid arthritis.Part 1:Literature Review1.Bone destruction is a major cause of disability in rheumatoid arthritis.Inhibiting disease activity,delaying or even blocking the process of bone destruction is an important goal in the treatment of rheumatoid arthritis.In recent years,the research on the treatment of rheumatoid arthritis bone destruction by Chinese medicine has gradually increased and achieved certain results.Chinese medicine research has gradually become an important direction to delay the bone destruction of rheumatoid arthritis.By combing the literature,the clinical and experimental aspects of traditional Chinese medicine to delay the bone destruction of rheumatoid arthritis are summarized.It is proposed that the long-term clinical study of rheumatoid arthritis in delaying bone destruction should be strengthened to provide evidence for clinical treatment.2.By analyzing and induction of my advisor treatment of rheumatoid arthritis,I summarized her academic thought of focusing on the combination of Chinese and western medicines to highlight their respective advantages;emphasizing internal and external combination therapy and comprehensive treatment are the best options for rheumatoid arthritis;she focuses on Food therapy,emphasis on life adjustment and taboo;and focus on enhancing patient compliance,improvement of chronic disease management,and continuously improve the experience of medication adherence in patients with rheumatoid arthritis.3.To summarize the value of X-ray in evaluation of bone destruction in rheumatoid arthritis and the clinical application of Sharp score.In recent years,skeletal and muscle ultrasonography,CT and MRI have gradually become an important means to evaluate joint inflammation and bone destruction in patients with rheumatoid arthritis.However,traditional X-ray examination is simple and inexpensive,and it is still an important and preferred imaging examination for the diagnosis and imaging evaluation of rheumatoid arthritis.The typical X-ray appearance of the patient is not only helpful for diagnosis,but also to assess the degree of joint destruction and clinical efficacy evaluation.The Sharp/van der Heijde score has broad application prospects for the study of bone destruction,including long-term follow-up of joint destruction,evaluation of clinical drug efficacy,and risk factors,predictors,and marker search for joint bone destruction.Part 2:Clinical ResearchObjective To observe and evaluate the changes of 5-year radiology in the treatment of bone destruction of rheumatoid arthritis by clearing away heat and activating blood circulation.Methods By open follow-up studies,28 cases of syndrome of damp heat and blood stasis resistance card activity of RA patients coming from July 2005 to July 2017 in the Department of Rheumatology,Guang’anmen Hospital,China Academy of Chinese Medical Sciences have been observed for five years.In order to evaluate the long-term effect of Clearing Heat and Activating Blood Recipe,the X-ray films of these patients’hands have been scored according to internationally accepted Sharp/van der Heijde score for consecutive five years before and after the treatment.Scores of joint space were scored in 30 areas of the x-rays of the hands,and erosion scores were scored in 32 areas and completed by two doctors.Statistical methods using SPSS 17.0 statistical analysis system.Measured data with normal distribution were expressed as mean ± standard deviation and t-test was used;non-normal distribution was expressed as median(interquartile range),using the Willcoxon rank sum test.Count data using Fisher’s exact test or chi-square test.P<0.05 was considered statistically significant.Result In this clinical study,28 patients with a qualified X-ray film were included in the plan,including 13 in the Chinese medicine group and 15 in the Chinese and Western medicine group.There was no significant difference in age and baseline disease between the two groups(P>0.05).1.Between the Chinese medicine group and the Chinese and western medicine group,there were no statistic differences in Sharp total score,joint clearance score and joint erosion score(P>0.05).2.Between Chinese medicine group and Chinese and western medicine group,there were no statistic differences in Sharp total score,joint clearance and joint erosion rate(P>0.05).The rate of radiological progression in most patients showed a decreasing trend.3.After five-year treatment,the baseline of the destruction group was significantly higher than the baseline of the non-destruction group in terms of Sharp total score,joint clearance and joint erosion(P<0.05).The baseline of the non-destruction group in terms of Sharp scores with scores greater than 10 were significantly less than those with baseline of the destruction group,while scores for total scores of 0 and 1-10 were lower than in the baseline of the destruction group(P<0.05).4.In 5 years of progress rate,patients with a baseline course greater than 2 years,the total score of Sharp group,joint space,joint erosion were greater than the baseline course less than or equal to 2 years group,the difference was statistically significant(P<0.05).patients with a baseline course less than or equal to 2 years group,the scores of sharp scores at 0 and 1-10 were all greater than patients with a baseline course greater than 2 years,while the scores with total scores greater than 10 were significantly less than those with>2 years of course(P<0.05).Conclusion1.Heat Clearing and Activating Blood Recipe can delay the progression rate of the bone destruction in RA patients for as far as five years.2.The combination of Heat Clearing and Activating Blood Recipe and MTX can delay the progression rate of the bone destruction rate in RA patients for as far as five years.3.The progression rate of the bone destruction in RA patients with bone destruction at baseline was greater than that of RA patients with no bone destruction at baseline.4.The rate of long-term bone destruction in RA patients with a baseline course greater than 2 years is greater than that of the baseline course less than or equal to 2 years RA patients.Part 3:Experimental Researchobjective The thesis is going to observe the effect of clearing away heat and activating blood circulation and its decomposed formulas on the serum TNF alpha and IL-6 in rats with rheumatoid arthritis,probe into the possible function of Clearing Heat and Activating Blood Recipe to delay bone destruction and the likely target of Jun Medicine and Chen Medicine(compositions of Clearing Heat and Activating Blood Recipe),and further explain the function basis of Clearing Heat and Activating Blood Recipe on RA bone protection.Methods The CIA rats model,set up the normal control group,model control group,the Methotrexate group,the treatment group of Heat Clearing and Activating Blood Recipe,the treatment group of Chlorogenic Acid(honeysuckle monomer),the treatment group of Astilbin(glabrous greenbrier rhizome monomer)and the treatment group of Tanshinone Ⅱ A(salvia miltiorrhiza monomer).6 rats in each treatment group.The level of TNF alpha and IL-6 in the rats’ serum have been compared and analyzed by Enzyme Linked Immunosorbent Assay.Result1.The serum TNF alpha and IL-6 in the model group was significantly higher than that in the normal group(P<0.05).The Methotrexate group,the treatment group of Heat Clearing and Activating Blood Recipe,the treatment group of Honeysuckle Monomer,the treatment group of Glabrous Greenbrier Rhizome Monomer and the treatment group of Tanshinone Monomer can lower the concentration of TNF alpha and IL-6 in CIA rat serum.There is a significant difference between these groups and model groups(P<0.05),but no significant difference among these groups(P>0.05).2.The effect of lowering TNF-alpha and IL-6 in the treatment group of Heat Clearing and Activating Blood Recipe is better than that of its decomposed formulas.The effects of its decomposed formulas can be observed as follows:Honeysuckle Monomer>Glabrous Greenbrier Rhizome Monomer>Tanshinone Monomer.Conclusion1.Heat Clearing and Activating Blood Recipe and its decomposed formulas can lower the level of serum inflammatory factors TNF-alpha and IL-6 in the CIA model rats.2.Both Jun Medicine and Chen Medicine(the compositions of Heat Clearing and Activating Blood Recipe)can lower the levels of TNF-alpha and IL-6.In terms of the effect,the compound is greater than the respective decomposed parts.3.Combined with clinical research that long-term adherence to Heat Clearing and Activating Blood Recipe for patients with rheumatoid arthritis results in slower progress in radiological progression of long-term bone destruction.By the means of lowering the level of serum inflammatory factors TNF-alpha and IL-6,Heat Clearing and Activating Blood Recipe may participate in delaying the progression of bone destruction in the long term.