Study On The Effect And Mechanism Of Jianpixiezhuo Formula On The Levels Of Serum URAT1 And GLUT9 In Gout Patients

1 Objective To observe the curative effect of Jianpi Xiezhuo method in patients with gout,and its effect on URAT1 and GLUT9 expression.To elucidate the relationship between URAT1 and GLUT9 with gouty arthritis.And to explore its mechanism from the perspective of uric acid transporter.2 Method2.1 Theoretical research Through literature retrieval and research,analysis the relationship between gout and uric acid transporter and TCM spleen deficiency and dampness stagnation,summed up the etiology and pathogenesis of uric acid transporter changes in gout patients with traditional Chinese medicine,clarify the mechanism of traditional Chinese medicine for treating gout with Jianpi Xiezhuo method.2.2 Clinical studies2.2.1 The changes and correlation of serum uric acid transporter in patients with gouty arthritis: To observe 60 cases of gout patients age,gender,disease duration,BMI,TCM syndrome value,quality of life(Short Form-36,SF-36),anxiety and Depression Scale(SAS,SDS)score,visual analogue scale,serum uric acid(UA),24 hours urinary protein quantity,24 hours urine uric acid,blood lipids,blood glucose,inflammation index and other laboratory indicators.Randomly selected 30 physical examination personnel which came from the physical examination center of Anhui Provincial Hospital of Traditional Chinese Medicine as the healthy control group.The gender,age of the control group matched with the gout patients.We used ELISA kits to detect changes of URAT1 and GLUT9 in healthy control group and gout patients,and also detected other laboratory indicators in gout patients: 24 hours urinary protein quantity,24 hours urine uric acid,urine uric acid,high sensitive C reaction protein(hs-CRP),erythrocyte sedimentation rate(ESR),blood glucose(GLU),triglyceride(TG),total cholesterol(T-CHOL),homocysteine(HCY),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),Cystatin C(Cys C),blood uric acid(UA),urine protein series,urinary albuminto-ereatinine ratio(ACR).The TCM syndrome value,visual analogue scale,SAS score,SDS score,life health questionnaire(SF-36)were observed.SPSS21.0 statistical software was used to analyze the correlation between uric acid transporter with the above indexes.2.2.2 Studies of Clinical efficacy: 60 cases of gout patients were randomly divided into study group(Jianpi Xiezhuo granules + Febuxostat Tablets)and the control group(Febuxostat Tablets)by each of the 30 cases.The URAT1,GLUT9,24 hours urinary protein quantity,24 hours urine uric acid,hs-CRP,ESR,TG,T-CHOL,HCY,LDL-C,HDL-C,Cys C,UA,urine protein series,ACR of two groups were detected.The changes TCM syndrome value,visual analogue scale,SAS score,SDS score,life health questionnaire(SF-36)were observed.SPSS21.0 statistical software was used to analyze the changes of uric acid transporter and the above indexes before and after the treatment.3 Results3.1 Theoretical results3.1.1 The functional defects of uric acid transporters play an important role in the occurrence and development of gout;3.1.2 The quality of life has became an important index to assess the clinical efficacy of gout;3.1.3 TCM syndrome of dampness stagnancy due to spleen deficiency which runs through the whole course of the gout;3.1.4 Jianpi Xiezhuo formula as a therapeutic method of traditional Chinese medicine which plays a key role in the treatment of gout.3.2 The results of clinical studies3.2.1 The studies on the change and correlation of uric acid transporter and 24 h PRO in gout patients.The serum levels of URAT1 and GLUT9 were significantly higher in gout patients compared with healthy control group.(P < 0.01).The serum URAT1 level was positively correlated with age and disease duration in gout patients(P < 0.05 or P < 0.01),the serum GLUT9 level was positively correlated with age and disease duration in gout patients(P < 0.01),24 h PRO was positively correlated with disease duration(P < 0.05).There were no significant correlation between URAT1,GLUT9 and 24 hPRO with BMI.Gout patients serum URAT1 and GLUT9 were positively correlated with GLU,TG,T-CHOL,LDL-C,HCY(P<0.05 or P<0.01),24 h PRO was positively correlated with HCY(P < 0.05).There was no significant correlation between URAT1,GLUT9 with HDL-C in gout patients,24 h PRO was not associated with GLU,TG,T-CHOL,HDL-C and LDL-C.The joint pain of the gout patients was positively correlated with the serum URAT1 and GLUT9(P <0.01).Joint swelling was positively correlated with URAT1,GLUT9,24 h PRO(P <0.01 or P <0.05).The flexion and extension of the joint was positively correlated with URAT1 and GLUT9(P <0.01).Gout stone was positively correlated with URAT1,GLUT9 and 24 h PRO(P <0.01).Joint heavy was positively correlated with URAT1,GLUT9(P <0.01).Mental exhaustion was positively correlated with URAT1,GLUT9(P <0.01).However,There was no significant correlation between24 h PRO with joint pain,the flexion and extension of the joint,joint heavy.The serum level of URAT1 was positively correlated with VAS score,SDS score and each dimension of the life quality(P <0.01 or P <0.05).GLUT9 was positively correlated with VAS scores,SDS scores,GH,PF,RP,SF,BP,VT,MH(P < 0.01 or P< 0.05).24 h PRO was positively correlated with VAS scores,GH,PF,RP,SF,BP,VT(P < 0.01 or P < 0.05).There was no significant correlation between SAS and URAT1,GLUT9,24 h PRO.URAT1 and GLUT9 were not associated with RE,24 h PRO was not associated with SDS scores,MH.The serum level of URAT1 was positively correlated with hs-CRP,ESR,UA and24 h UUA in patients with gout patients(P < 0.01 or P < 0.05).The serum level of GLUT9 was also positively correlated with hs-CRP,ESR,UA and 24 h UUA in patients with gout patients(P < 0.01 or P < 0.05).Beside,24 h PRO was positively correlated with hs-CRP,ESR,UA and 24 h UUA(P < 0.01 or P < 0.05).3.2.2 Clinical efficacy on the treatment of gouty arthritis with Jianpi Xiezhuo formula After the treatment,the total effective rate of the two group were 83.33(4)and 76.67(4),no statistically significant difference(P(29)0.05).However,the clinical cure rate of treatment group(20(4))was significantly higher than the control group(6.67(4))(P <0.05).3.2.3 The effect of Jianpi Xiezhuo formula on uric acid transporter and 24 h PRO in gout patients.After treatment,the URAT1,GLUT9 and 24 h PRO of the two groups were significantly lower than those before treatment(P < 0.01).The treatment group was significantly better than the control group in reducing URAT1,GLUT9 and 24 h PRO(P < 0.05 or P < 0.01).3.2.4 The effect of Jianpi Xiezhuo formula on hs-CRP?ESR?UA?24h UUA in gout patients.After treatment,the hs-CRP,ESR and UA of the two groups decreased significantly(P< 0.01),and the 24 h UUA was significantly increased(P < 0.01).The treatment group was significantly better than the control group in reducing hs-CRP,ESR,UA(P < 0.05 or P < 0.01),and the treatment group was also significantly better than the control group in promoting the urinary excretion of uric acid(P < 0.01).3.2.5 The effect of Jianpi Xiezhuo formula on blood glucose and blood lipid in gout patients.The serum levels of GLU,TG,T-CHOL,LDL-C and HCY of the treatment group were significantly lower than those before treatment(P < 0.01 or P < 0.05).The LDL-C of treatment group of there has obvious change,besides,there were no significant changes of blood glucose and blood lipid in control group.After treatment,the GLU,TG,T-CHOL and HCY of the treatment group were significantly lower than those of the control group(P <0.05 or P <0.01).HDL-C and LDL-C had no significant changes in the two groups after treatment.3.2.6 The effect of Jianpi Xiezhuo formula on urine protein series,ACR and Csy-C.The ALBU,a1-MG,b2-MG,Csy-C and ACR of treatment group were significantly lower than that before treatment(P < 0.01 or P < 0.05).There were no significant changes about Ig GU and TRFU in the treatment group after treatment,and the urine protein series,ACR and Csy-C of control group had no significant changes after treatment.After treatment,the a1-MG,b2-MG,Csy-C and ACR of treatment group were significantly lower than the control group(P < 0.01),However,the Ig GU,TRFU and ALBU had no significant changes in the two groups after treatment.3.2.7 The effect of Jianpi Xiezhuo formula on TCM syndrome value.The TCM syndrome value of two groups had no significant difference before treatment(P(29)0.05).After treatment,the TCM syndrome value of the two groups reduced significantly(P < 0.01).The treatment group was more effective in improving joint pain,joint swelling,gout stone and mental exhaustion than the control group after treatment(P <0.05 or P <0.01).Meanwhile,the two groups had no significant difference when improving the flexion and extension of the joint and joint heavy(P(29)0.05).3.2.8 The effect of Jianpi Xiezhuo formula on VAS scores,anxiety and depression scores,quality of life scores.The VAS scores,anxiety and depression scores,quality of life scores of two groups had no significant difference before treatment(P(29)0.05).After treatment,VAS scores,SAS scores and SDS scores of the two groups reduced significantly(P <0.05 or P <0.01).The each dimension of the life quality reduced significantly in the two groups(P < 0.01).The treatment group was more effective in improving SAS scores,SDS scores,GH,RP,SF and MH than the control group after treatment(P <0.05 or P<0.01).4 Conclusion4.1 The levels of serum URAT1 and GLUT9 were significantly increased in gout patients.The URAT1 and GLUT9 in gout patients were closely related to age,disease duration,carbohydrate and lipid metabolism.The URAT1 and GLUT9 were closely related to the degree of oint symptoms,serum uric acid and inflammation index.4.2 Jianpi Xiezhuo formula has a downward effect for URAT1 and GLUT9,correct URAT1 and GLUT9,and inhibit the URAT1,GLUT9 high expression.4.3 Jianpi Xiezhuo formula can effectively relieve the patient's joint pain,swelling and gout stone and other general body joint symptoms,and has the effect of strengthening spleen and removing turbid.It can improve patient's physical and mental health,improve patient quality of life.4.4 Jianpi Xiezhuo formula can effectively reduce the level of serum uric acid,promote the excretion of uric acid,reduce the hs-CRP,ESR and other inflammatory indicators.4.5 Jianpi Xiezhuo formula can reduce 24 h PRO,ALBU,?1-MG,?2-MG,Csy-C and ACR which has preventive and therapeutic effect on the early renal damage caused by gout or hyperuricemia.4.6 The possible pathogenesis of Jianpi Xiezhuo formula on treatment for gout based on the uric acid transpor.Uric acid transporters are involved in the transport process of uric acid metabolism,and have a direct regulatory effect on the level of serum uric acid.URAT1 and GLUT9 play a dual role in mediating the transport of uric acid.If the drugs prescription with their affinity can be used,uric acid can be effectively excreted.In addition,urate acid transporters can regulate the inflammatory response indirectly by regulating serum uric acid concentration.Jianpi Xiezhuo formula has a downward effect for URAT1 and GLUT9,inhibit the URAT1,GLUT9 high expression,so as to reduce the blood uric acid,promote the excretion of uric acid and reverse the damage of kidney.