| Objective: This study aim to:(1)Study whether smilax riparia,a Chinese hebal named Niu Wei Cai can enhance the efficacy of allopurinol;(2)Study whether Pallidifloside D,an active compound from Smilax riparia,can enhance the efficacy of allopurinol;(3)Systematically analysis the efficacy and safety of the combination of allopurinol and benzbromarone;(4)Systematically analysis Association of rs2231142 polymorphism in the ABCG2 gene with the prevalence of gout in Asian populations.Methods: 1? In this study,fourty hyperuricemia mices model induced by potassium oxonate was randomly divided into five groups:(1)control group(Control);(2)model group(Model);(3)allopurinol group(AP);(4)smilax riparia group(SRS);(5)smilax riparia + allopurinol group(SRS+AP).After drug intervention for a week,serum,urine and renal cortex were collected,and UA,Cr,BUN and XOD levels were measured through the appropriate kits.Then URAT1,GLUT9 and OAT1 in the mouse kidney tissue were measured by means of the WST method.2? Firstly,the active ingredient Pallidifloside D compound was extracted from the herb.Then,the hyperuricemi mouse model was established.After drug intervention for a week,serum,urine and renal cortex were collected,and UA,Cr,BUN and XOD levels were measured through the appropriate kits.Then URAT1,GLUT9 and OAT1 in the mouse kidney tissue were measured by means of the WST method.3? We have searched the domestic and foreign databases from building issue to February in 2018.The key words for searching English are: allopurinol,benzbromarone,combination,combined,gout,hyperuricemia,hyperuricaemia;Chinese keywords are translated by the English keywords.All studies retrieved were screened for final inclusion in the literature and data were extracted and analyzed by Rev Man 5.3 and STATA 11.0 software.4? We have searched the domestic and foreign databases from building issue to February in 2018.The key words for English are: ABCG2,Q141 K,gout,hyperuricemia,hyperuricemia,polymorphism,rs2231142;Chinese keywords are translated by the English keywords.All studies retrieved were screened for final inclusion in the literature and data were extracted and analyzed by Rev Man 5.3 and STATA 11.0 software.Results: 1? The results show that the combination of smilax riparia and allopurinol can indeed enhance the effect of allopurinol,significantly reduce serum uric acid level,increase urine uric acid level,and reduce Scr level.In addition,the fraction excretion of uric acid(FEUA)supports this synergistic effect.The combination of allopurinol and SRS significantly reduced serum and kidney XOD activity and enhanced allopurinol's ability to regulate URAT1,GLUT9,and OAT1 proteins.2? The experimental results showed that Pallidifloside D,an active ingredient from smilax riparia,can synergize with allopurinol to enhance the effect of lowering uric acid.It has the same tropism of lowering uric acid with smilax riparia.3? A total of 7 studies including 520 participants were included in the meta analysis.The results showed that the pooled SMD was-1.326,95% CI(-2.121--0.531),Z = 3.27,P <0.05,indicating that the combination of benzbromarone and allopurinol has better efficacy.In terms of safety,only three studies were mentioned with adverse reactions in a small number of patients,and the data were not statistically significant.4? A total of 13 studies including 7493 participants were included in the meta analysis.The result showed that there was a relevance between ABCG2(rs2231142 A/C)gene polymorphism and the occurrence of gout(All models p>0.001).A allele(OR: 2.438,95% CI: 2.438~3.362,P ? 0.00001)Or homozygous gene AA(OR: 4.054,95% CI: 3.404~4.829,P ? 0.00001)was associated with susceptibility of gout,while the risk of gout was significantly lower in people carrying the CC genotype(OR: 0.418,95% CI: 0.346 to 0.505,P ? 0.00001).Conclusion: 1? Compared to the use of allopurinol alone,the combination of smilax riparia or Pallidifloside D compound had a better urinary excretion activity.Our data may have potential value in the clinical practice of treating gout and other hyperuricemia symptoms.2? The results of the analysis showed that the combination of allopurinol and benzbromarone was superior to the use of allopurinol alone.In terms of safety,the combination of the two drugs did not increase the occurrence of adverse reactions.Therefore,our study has a certain significance in clinical application.3? The results showed that the genetic polymorphism of Q141K(rs2231142)locus in ABCG2 gene not only increased the incidence of gout in Asian populations,but also the genotype A of rs2231142 may be an important factor in the morbidity of gout and may exist diversity in gender and regions.It has certain clinical significance in prevention and effective control of gout attacks. |
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