| Objective1.By systematically collating and studying the literature,this paper reviews the definition of metabolomics,commonly used detection technology,detection process,etc.,and focuses on the application of metabolomics in the study of gout and hyperuricemia.2.To clarify the abnormal metabolic mechanism of hyperuricemia by metabonomics,and to clarify the metabolic pathway and related metabolic markers of compound Tufuling granule in the treatment of hyperuricemia,so as to provide evidence for the early prevention and treatment of hyperuricemia.3.To observe the clinical efficacy and safety of Compound Tufuling Granule in the treatment of asymptomatic hyperuricemia,and to carry out gene polymorphism typing.To observe the effect of gene polymorphism on the hypouric acid effect of Compound Tufuling Granules,and to provide basis for clinical treatment.Methods1.This review reviews the definition of metabolomics,common detection techniques,detection processes and so on,focusing on the application of metabolomics in gout and hyperuricemia by consulting relevant literature at home and abroad.2.The experimental research is divided into two parts.The first part:30 rats were randomly divided into normal group,hyperuricemia model group and low,medium and high dose group,6 rats in each group.At the beginning of the experiment,all rats except the normal group were intraperitoneally injected with potassium oxalate 100mg/kg,while hypoxanthine 500mg/kg was intragastrically administered to prepare hyperuricemia model.The above dosage was given at 8:00 a.m and lasted until the end of the experiment.The whole experiment lasted for 19 days.Starting from the 4th day of model building,the rats were given low(1g/kg),medium(2g/kg)and high dose groups(4g/kg)of Compound Tufuling Granules after 1 hour of model building agent.The blood was collected from the orbital of the rats on the 1st,4th,7th,10th,13th,16th and 19th days.The second part:32 SD rats were randomly divided into normal group,hyperuricemia model group,compound Tufuling granule and allopurinol tablet group,8 rats in each group.After the beginning of the experiment,all rats except the normal group used the same method to induce hyperuricemia model.The whole experiment lasted for 10 days.On the 4th day of modeling,the rats were given compound Tufuling granules(4g/kg)solution one hour after the injection of moulding agent.Two hours after the last drug administration(10 days),the orbital blood was collected under respiratory anesthesia in rats.The blood was stored in non-anticoagulant tube,centrifuged,and stored in-80 degree C refrigerator for metabolomics test.Two ml blood was collected from abdominal aorta.After centrifugation,the levels of TNF-α and IL-1β in serum of rats were detected by Enzyme-linked immunosorbent assay(Elisa).The serum uric acid,creatinine and urea nitrogen were measured in the remaining supernatant.3.Clinical study included 79 patients with hyperuricemia.They were randomly divided into experimental group(39 cases)and control group(40 cases).The experimental group was treated with Compound Tufuling Granules and the control group was treated with allopurinol tablets or benzbromarone capsules for 8 weeks.Intravenous blood samples were taken from two groups of patients and DNA was extracted.15 SNP loci were detected:rs11942223,rs3775948,rs11722228,rs2231142,rs1801133,rs606458,rs1050152,rs129861,rs12800450,rs9321453,rs780094,rs1057910,rs1799853,rs92625700,rs9263726.The genotypes of these loci were classified into uric acid deficiency type,kidney hypernegativity type.Logistic regression analysis was used to analyze the effects of gene polymorphism on uric acid-lowering efficacy,gastrointestinal tract,liver and kidney function,blood system,kidney stones and family genetic history.Results1.In the first part of the experiment,the level of serum uric acid in the model group was significantly higher than that in the normal group on the 1st,4th,7th,10th,13th,16th and 19th day(P<0.05).On the 4th,7th,10th,13th,16th and 19th day,the level of serum uric acid in the model group was significantly lower than that in the model group(P<0.05).The level of serum uric acid in the high-dose group was lower than that in the middle-dose group(P<0.05).2.In the second part of the experiment,the levels of serum uric acid,creatinine,urea nitrogen,TNF-α and IL-1 βin the model group were significantly higher than those in the normal group(P<0.05).The levels of serum uric acid,creatinine,urea nitrogen,TNF-a and IL-1β in the compound Tufuling granule group were significantly lower than those in the model group(P<0.05).Seven potential differential metabolites associated with hyperuricemia were screened by metabolomics.It is divided into galactic acid,pantothenic acid,whey nucleoside,whey acid,uric acid,Phenylpyruvate and goose deoxycholic acid.The corresponding metabolic pathways are pentose and glucuronic acid conversion,pantothenic acid and coenzyme A biosynthesis,pyrimidine metabolism,purine metabolism,phenylalanine metabolism and bile secretion.These pathways are linked to each other through pyrimidine metabolism and pantothenate and coenzyme A biosynthesis.Uracil and acetyl coenzyme A are two key node molecules in the metabolic network.Hyperuricemia is mainly associated with metabolic disorders of cholesterol,amino acids,lipids,vitamins and glucose.Compound Tufuling Granule can successfully reverse these seven potential differential metabolites,and regulate the metabolic network by these two key node molecules.Ultimately,it can reduce uric acid and protect renal function by regulating the metabolism of cholesterol,amino acids,lipids,vitamins and glucose.3.Clinical research:Before treatment,there was no significant difference in serum uric acid level between the two groups(P>0.05).After treatment,the serum uric acid level of the two groups was significantly lower than that before treatment(P<0.05).There was no significant difference in uric acid value between the two groups after treatment(P>0.05).Chi-square test showed that there was no significant difference in the proportion of patients with uric acid 05).The clinical factors were included in the covariate to correct.The genetic polymorphisms of CYP2C9(rs105791),SLC2A9(rs11722228),PDZK1(rsl29861),MTHFR(rs1801133),ABCG2(rs2231142),SLC2A9(rs3775948),SF1(rs606458),GCKR(rs780094),HLA-B5801(rs9262570),HLA-B5801(rs9263726)and CYP2C9(rs1799853)were divided into two groups.There was no significant difference in drug efficacy,history of renal calculi and family history(P>0.05).After medication intervention,it was found that mixed genotyping had an increased toxicity and side effects on glutamic acid,glutamic oxaloacetic transaminase,creatinine and urea nitrogen(P<0.05),but had no significant effect on the toxicity and side effects of blood system and other systems(P>0.05).Conclusion1.In animal experiments,Compound Tufuling Granule can significantly reduce the level of serum uric acid in hyperuricemia model rats,and has the effect of anti-inflammation and protection of renal function.2.Compound Tufuling Granule can reduce uric acid,anti-inflammation and protect renal function by regulating the metabolic levels of cholesterol,amino acids,lipids,vitamins and glucose.Its metabolic mechanism may be related to regulating the two key node molecules of uracil and acetyl coenzyme A and the two key metabolic pathways of pyrimidine,pantothenate and coenzyme A biosynthesis.3.In clinical experiments,Compound Tufuling Granule can significantly reduce the level of serum uric acid,and has high safety.4.Gene polymorphism has no significant effect on the efficacy of drugs.Mixed genotypes of gene polymorphism are a protective factor for mild liver and kidney dysfunction. |
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