Study On The Effect And Mechanism Of Jianpixiezhuo Formula On Thelevels Of Serum NLRP3?IL-1? And IL-10 In Gout Patients

1 Objective To observe the effect of Jianpi Xiezhuo method in patients with gout curative and the effect of cytokines NLRP3,IL-1?and IL-10.And to explore the mechanism of action from the persp ective of cytokines.2 Method 2.1 Theoretical researchAnalyzes the relationship between gout and NLRP3,IL-1? and IL-10.and TCM spleen deficiency and dampness stagnation,To explore the etiology and pathogenesis of the changes of NLRP3,IL-1? and IL-10 in gout patients.clarify the theoretical basis of the method of invigorating spleen and removing turbidity in the treatment of gout.2.2 Clinical studies 2.2.1 Changes of NLRP3,IL-1? and IL-10 in gout patients and their correlation:To observe 60 cases of early gouty nephropathy age,course of disease,sex,BMI,integral value of TCM symptoms,quality of life(Short Form-36,SF-36),anxiety and depression scale(SAS,SDS),pain VAS score,creatinine(CREA),urea nitrogen(BUN),uric acid(UA),24 hour uric acid(24hUUA),blood lipid and blood sugar series,inflammatory indicatorsand other laboratory indicators.In the control group,20 health examinees were selected from the physical examination center of Anhui Traditional Chinese Medicine Hospital,with the same sex and age.ELISA kit was used to detect NLRP3,IL-1?,IL-10,UA,24 h UUA,blood sugar and lipid series.The TCM symptom grading score,pain VAS score,SAS score,SDS score and life health questionnaire(SF-36)of gout patients were observed.SPSS 22.0 statistical software was used to analyze the correlation between NLRP3,IL-1?,IL-10 and the above indicators.2.2.2 Sixty patients with gout were randomly divided into treatment group(Jianpi Xiezhuo Decoction + febustar)and control group(febustar)with 30 cases each.NLRP3,IL-1beta and IL-10 were detected in the two groups.To observe the TCM symptom grading score,pain VAS score,SAS score,SDS score,life and health questionnaire,etc.SPSS 22.0 was used to analyze the changes of NLRP3,IL-1beta,IL-10 and many indexes in the two groups before and after treatment.3 Results 3.1 Theoretical results 3.1.1 NLRP3,IL-1beta and IL-10 play an important role in the occurrence and development of gout.3.1.2 Quality of life has become an important index to evaluate the efficacy of gout.3.1.3 Spleen deficiency and dampness turbidity are the basic etiology and pathogenesis of gout,which runs through the course of gout.3.1.4 The method of invigorating spleen and removing turbidity is the key treatment of gout in traditional Chinese medicine.3.2 The results of clinical studies 3.2.1 Changes of NLRP3,IL-1? and IL-10 in gout patients and their correlation.Compared with healthy control group,NLRP3,IL-1? and IL-10 in gout group were generally increased(P < 0.01).NLRP3 was positively correlated with BMI in gout patients(P < 0.05),but not with age and course of disease;IL-1? was positively correlated with age(P < 0.01),but not with course of disease and BMI;IL-10 was negatively correlated with course of disease(P < 0.05),but not with age and course of disease.NLRP3 was positively correlated with GLU,TG,T-CHOL and LDL-C in gout patients(P < 0.05 or P < 0.01),but not with HDL-C;IL-1? was positively correlated with TG and T-CHOL(P < 0.01);IL-10 was negatively correlated with T-CHOL(P < 0.05),and positively correlated with HDL-C(P < 0.01).Joint pain in gout patients was positively correlated with NLRP3 and IL-1?(P < 0.01);joint swelling was positively correlated with NLRP3 and IL-1?(P < 0.01),negatively correlated with IL-10(P < 0.05);joint flexion and extension was positively correlated with IL-1?(P < 0.01);had no significant correlation with NLRP3 and IL-10;gout stone was positively correlated with NLRP3(P < 0.01),negatively correlated with IL-10(P < 0.05),and had no correlation with IL-1beta.Joint stress was positively correlated with NLRP3 and IL-1?(P < 0.05),negatively correlated with IL-10(P < 0.01),positively correlated with mental fatigue and IL-1?(P < 0.05 or P < 0.01),negatively correlated with IL-10(P < 0.05),but not with NLRP3.NLRP3 was positively correlated with VAS pain score(P < 0.05),but not with GH,PF,RP,SF,BP,VT and MH in SAS,SDS and quality of life.IL-1? was positively correlated with VAS pain score,SAS,SDS(P < 0.05),and negatively correlated with GH,RP,RE,SF,VT and MH(P < 0.05 or P < 0.01).The correlation was positive with PF,RP,SF,BP and MH(P < 0.05 or P < 0.01),but not with VT,GH and RE.NLRP3 was positively correlated with hs-CRP,ESR and UA(P < 0.05),negatively correlated with 24hUUA(P <0.05),positively correlated with hs-CRP,ESR and UA(P <0.05),negatively correlated with 24hUUA(P <0.05),negatively correlated with hs-CRP,ESR and UA(P < 0.05 or P < 0.01),and positively correlated with 24hUUA(P < 0.01).3.2.2 Clinical effect of Jianpi Xiezhuo Formula on gout The total effective rates of the two groups were 86.67% and 76.67%,respectively,with no significant difference(P > 0.05),but the clinical recovery rate of the treatment group(33.33%)was significantly higher than that of the control group(13.33%)(P < 0.05).3.2.3 Effect of Jianpi Xiezhuo Formula on NLRP3,IL-1? and IL-10 in Gout Patients After treatment,the levels of NLRP3 and IL-1? in the treatment group and the control group decreased significantly(P < 0.01)and IL-10 increased(P < 0.01),while the levels of NLRP3,IL-1? and IL-10 in the treatment group were significantly higher than those in the control group(P < 0.05 or P < 0.01).3.2.4 Effect of Jianpi Xiezhuo Formula on UA,24 hUUA,hs-CRP and ESR in gout patients After treatment,UA,ESR,hs-CRP decreased and 24 hUUA increased in both groups(P < 0.01).Compared with the control group,UA,ESR and hs-CRP levels in the treatment group were significantly lower than those in the control group(P < 0.05 or P < 0.01),and 24 hUUA excretion in the treatment group was significantly better than that in the control group(P < 0.05).3.2.5 After treatment,GLU,TG,T-CHOL,LDL-C decreased in the treatment group(P < 0.01),while HDL-C did not change significantly in the control group;blood sugar,lipid and other indicators did not change significantly in the control group;compared with the control group,GLU,TG,T-CHOL,LDL-C decreased more significantly in the treatment group(P < 0.05 or P < 0.01),HDL-C did not differ significantly between the two groups after treatment.3.2.6 Effect of Jianpi Xiezhuo Formula on TCM Syndromes of Gout Patients After treatment,there was no significant difference in the scores of TCM symptoms between the two groups before treatment(P > 0.05);after treatment,the scores of TCM symptoms in the two groups decreased significantly(P < 0.01);after treatment,the pain,swelling,gout stone and mental fatigue in the treatment group were more obvious than those in the control group(P < 0.05 or P < 0.01);while after treatment,the joint flexion and extension of the two groups were disadvantageous and the joint was heavily concerned.There was no significant difference in face area(P > 0.05).3.2.7 Effect of Jianpi Xiezhuo Formula on VAS Score,Anxiety and Depression Score and Quality of Life Score of Gout Patients.There was no significant difference in VAS score,anxiety and depression score and quality of life scores between the two groups before treatment(P > 0.05);VAS pain score decreased significantly after treatment in both groups(P < 0.01),SDS and SAS levels decreased in the treatment group(P < 0.05 or P < 0.01),and GH,RF,RP,RE,SF,BP,VT and MH levels increased in all dimensions of quality of life(P < 0.01).After treatment,the levels of GH,RF,RP,RE,SF,BP,VT and MH in the control group increased(P < 0.01),while the levels of SDS and SAS did not change significantly.After treatment,the VAS pain score and SAS in the treatment group decreased more significantly(P < 0.05 or P < 0.01),and GH,RE,SF and MH increased more significantly(P < 0.05 or P < 0.01)than those in the control group.4 Conclusion 4.1 The levels of NLRP3,IL-1? and IL-10 in gout patients increased significantly.4.2 The levels of NLRP3,IL-1? and IL-10 in gout patients were closely related to age,course of disease,BMI,blood sugar,lipid,UA,joint symptoms and inflammatory indexes.4.3 The method of invigorating spleen and removing turbidity can significantly increase the level of serum IL-10 and decrease the levels of NLRP3 and IL-1? in patients with pain.4.4 Jianpi Xiezhuo Formula can reduce blood uric acid and promote 24 hour uric acid excretion,and reduce inflammatory indicators such as hs-CRP and ESR in gout patients.4.5 Jianpi Xiezhuo Formula can alleviate joint pain,swelling,gout stone and other systemic joint symptoms,and has the function of invigorating the spleen and relieving turbidity.It can improve the physical and mental health of patients and improve the quality of life of patients.4.6 Gout is an inflammatory reaction mediated by MSU crystals.If uric acid metabolism is out of balance,MSU crystals will precipitate.MSU crystals are engulfed by immune cells and NLRP3 is activated.There are many activation pathways,and then release IL-1beta,release a large number of inflammatory mediators,in this context,there will be inflammation cascade amplification.This can lead to the onset of gout arthritis.At the same time,the accumulation of pro-inflammatory cytokines and the increase of IL-10 production promote the balance of pro-inflammatory and anti-inflammatory cytokines and the recovery of inflammation.The method of invigorating spleen and removing turbidity can reduce the activation of NLRP3 inflammatory body,reduce the level of IL-1beta,increase the level of IL-10,protect the kidney,promote the excretion of uric acid,and alleviate the general symptoms of gout.Therefore,the method of invigorating the spleen and removing turbidity has a remarkable effect,which makes the patients have a higher quality of life.