Study On Mechanism Of Si Shen Decoction In Treating Gouty Arthritis Based On Xuanfu Theory

1.The Theoretical Study on Treatment of Gouty Arthritis with Si Shen Decoction Objective:To explore the theoretical connotation of TCM Sishen decoction in the treatment of gouty arthritis based on Xuanfu Theory.Methods:According to the origin of Xuanfu theory,the theoretical connotation of traditional Chinese medicine Sishen decoction for gouty arthritis treatment was discussed in this paper,via analyzing the related and similar nouns of Xuanfu,the physiology,pathology and treatment law of Xuanfu,and the pathogenesis and development of arthralgia syndrome from the perspective of Xuanfu.Results:Xuanfu is the smallest structural unit and functional unit of the human body.It has the functions of ventilating qi,blood and body fluid,infiltrating the organs.The Xuanfu related diseases are divided into three categories:Xuanfu occlusion,non-consolidation of Xuanfu,Xuanfu paralysis,among them Xuanfu occlusion is the most common,which need the method of opening the Xuanfu.When opening the Xuanfu,it can be compatible with medicine that can dispel the wind according to the circumstances.Wind-dispelling medicine can adjust the qi and raise the yang,resolve the dampness and activate the blood,lead the medicine to reach the Xuanfu,remove the depression of the Xuanfu,and solve the occlusion of Xuanfu,and play a unique synergistic role.It is an important index to judge whether the Xuanfu is open or not to observe the sweat in the pathological condition of the xuanfu.Body xuanfu occlusion,defensive Yang was obstructed wihle ying Yin runs stagnantly,with the pore obstructed,so there’s no sweat.After the treatment,Xuanfu get clear,qi,blood and body fluid can run smoothly,so normal sweat recoveries.The etiology,pathogenesis,symptoms and treatment of arthralgia syndrome are closely related to obstruction of Xuanfu.Gouty arthritis as a kind of arthralgia syndrome,also caused by the obstruction of Xuanfu.Sishen decoction has the function of opening Xuanfu,and its TCM connotation of treating gout arthritis lies in clearing heat,regulating qi,activating blood circulation,body fluid circulation and removing phlegm,etc.Conclusion:Sishen decoction can be used to treat gouty arthritis by opening Xuanfu and dredging qi,blood and body fluid.2.Network pharmacological analysis of sishen decoction in the treatment of gouty arthritisOBJECTIVE:to predict the potential targets of sishen decoction in the treatment of gout arthritis by network pharmacology,and to discuss the mechanism.Methods:1.Gouty Arthritis was used to retrieve disease related targets of gouty arthritis in OMIM database;2.Based on the Batman-TCM database,the drug-related targets of five traditional Chinese medicines in sishen decoction were retrieved;3.Map the predicted disease and drug-related targets into STRING software,construct the Protein-Protein Interaction(PPI)network,and import the results into Cytoscape3.6.0 for topological structure value calculation,so as to obtain the drug-disease core target and perform network;4.The selected drug-disease targets were introduced into DAVID analysis for bioinformatics analysis to enrich the KEGG pathway,and the mechanism of sishen decoction in the treatment of gout arthritis was preliminarily discussed.Results:1.425 disease-related genes and 467 drug-related genes of sishen decoction were predicted.2.Via setting the Degree,Closeness,Betwness centrality greater than or equal to the average value,191 sishen decoction drug-disease core targets,3326 interaction pairs were discovered.3.Through pathway enrichment analysis,43 signaling pathways related to the treatment of gout arthritis by sishen decoction were obtained.The top 10 pathways include the apoptotic pathway,the Toll-like receptor signaling pathway,the type Ⅱ diabetes pathway,the cancer pathway,the cytokine-cytokine receptor interaction pathway,the prostate cancer pathway,the sputum metabolism,the pancreatic cancer pathway,Fc epsilon RI signaling pathway,arginine and proline metabolic pathways.4.Sishen decoction can exert anti-inflammatory and immunomodulatory effects through various ways.Lots of genes were enriched in the Toll-like receptor signaling pathway gene associated with inflammation,which can be used as an important pathway for the treatment of gouty arthritis.Conclusion:sishen decoction may play a role in the treatment of gout arthritis by regulating TLR4/MyD88/NF-kB signaling pathway.3.Experimental study on the anti-inflammatory effect of sishen decoction on gout arthritis induced by MSU in rats and its mechanismOBJECTIVE:To study the effects of different doses of sishen decoction on the degree of joint swelling and the contents of il-1,il-6 and TNF-a in the serum of gout arthritis rats induced by MSU,and to verify its anti-inflammatory effect.The effect of TLR4,MyD88,NF-kB-p65 protein expression on synovial tissue of joints was studied.METHODS:60 Wistar male rats were randomly divided into blank control group,model group,diclofenac sodium sustained release tablet group(0.0135g/kg),low dose sishen decoction group(3.87g/kg),medium dose sishen decoction group(11.61g/kg),and high dose sishen decoction group(34.83g/kg),with 10 rats in each group.Except for the blank group,the other 5 groups of rats were induced to model with sodium urate crystals.After the model was established,the rats were given drugs respectively once a day for 7 days.Observe the general condition of rats,ankle swelling degree at 4h,8h,24h,48h and 72h after molding,serum il-1,il-6,TNF-a,uric acid,liver function(ALT,AST),renal function(UREA,CREA);Expression of TLR4,MyD88 and NF-kB-p65 in ankle synovial tissue.RESULTS:1.Sishen decoction can reduce the degree of ankle swelling of rats with gout arthritis at 8h-72h in each dose group.Compared with western medicine group,sishen decoction has a relatively slow effect,but the continuous observation shows that its effect is the similar to that of western medicine group(P>0.05).The efficacy of sishen decoction was better in medium and low dose group,but worse in high dose group.2.Pathology showed that each group of sishen decoction improved the infiltration,synovial hyperplasia,degeneration and necrosis of ankle arthritis cells in rats with gouty arthritis to varying degrees.3.The serum levels of il-1,il-6 and TNF-a in each group were decreased by sishen decoction(P<0.01,P<0.05).The protein expressions of TLR4 and NF-kB-p65 in the synovial tissue of ankle joint were decreased in each group to different degrees(P<0.01,P<0.05),but MyD88 protein expression was not significantly affected.Conclusion:1.Sishen decoction has anti-inflammatory effect on gout arthritis induced by MSU in rats;2.The mechanism of sishen decoction in the treatment of gout arthritis in rats may be related to the regulation of TLR4/NF-kB pathway.