| Objective:Through non-targeted liquid chromatography mass spectrometry(LC/MS)and bioinformatics analysis,this study analyzed the changes of plasma metabolic spectrum in patients with acute gout before and after taking Chuanhu anti-gout mixture,and explored the mechanism and target of drug treatment.Method:A total of 30 patients with acute gout who attended the Affiliated Hospital of Qingdao University and 30 healthy people who were examined by physical examination center were selected and divided into gout group and healthy control group respectively.The subjects’ age,gender,height,weight,current medical history and medication were recorded in detail.Fasting blood samples were collected from all subjects for laboratory tests,and the indicators included uric acid,creatinine,total cholesterol,triglycerides,C reactive protein and erythrocyte sedimentation rate.The patients in the gout group were treated with Chuanhu anti-gout mixture for 2 weeks,and the changes of clinical and laboratory indexes were counted,and plasma samples were collected.Metabolomic detection of plasma samples was performed by LC/MS technology.Through quality control,the pretreatment of the experiment and the stability of the mass spectrometry system were analyzed and evaluated.After qualified,the differential metabolites wound be found through the qualitative,quantitative analysis and data analysis of metabolites,and the differential metabolites wound be screened.Finally,we explored the targets and mechanisms of action through metabolic pathway enrichment analysis.Results:1.Results of general clinical data.Compared with the healthy control group,the levels of body mass index,uric acid,TG,CRP and ESR in gout group were significantly higher(p < 0.05).There was no significant change in sex ratio,Cr and TC between the groups.The levels of uric acid,CRP and ESR in gout group decreased significantly after treatment with Chuanhu anti-gout mixture(p <0.05).2.Gout metabolomics analysis.A total of 154 differential metabolites between gout group and healthy control group met the screening criteria of variable importance of projection(VIP)> 1 and p< 0.1.Compared with the healthy control group,98 differential metabolites such as uric acid,Cr,TC,proline and L-isoleucine were up-regulated in gout group.Docosahexaenoic acid,eicosadienoic acid,sphingosine 1-phosphate,PC(22:5(4Z,7z,10 z,13z,16Z)/ 16:1(9z)),PC(18:2(9z,12z)/ 20:2(11z,14z))and PC(22:6(4Z,7z,10 z,13z,16 Z,19Z)/ 16:0)were down regulated.At the same time,43 different metabolites related to the treatment of gout with Chuanhu Qutong mixture were found.After gout treatment,19 differential metabolites such as uric acid,bilirubin,4e,15 bilirubin IXA,PC(16:1(9z)/ p-18:0)were down regulated,allopurinol,allopurinol-1-ribonucleoside,hypoxanthine,inosine,PC(22:5(4Z,7z,10 z,13z,16Z)/ 16:1(9z)),PC(18:2(9z,12z)/ 20:2(11z,14z))PC(22:6(4Z,7z,10 z,13z,16 Z,19Z)/ 16:0)and SM(d18:0 / 16:1(9z))were up-regulated.Therefore,Chuanhu anti-gout mixture can reverse the abnormal expression of the following metabolites related to gout: uric acid,PC(22:5(4Z,7z,10 z,13z,16Z)/ 16:1(9z)),PC(18:2(9z,12z)/ 20:2(11z,14z)),PC(22:6(4Z,7z,10 z,13z,16 Z,19Z)/ 16:0),etc.The results of metabolic pathway enrichment analysis showed that the metabolic disorder of gout patients mainly involved the following pathways: choline metabolism in cancer,sphingolipid signaling pathway,ether lipid metabolism,sphingolipid metabolism,linoleic acid metabolism,primary bile acid biosynthesis,glycerol phospholipid metabolism,aminoacyl t RNA biosynthesis,etc.The treatment of gout with Chuanhu antigout mixture is mainly related to choline metabolism in cancer,purine metabolism and glycerol phospholipid metabolism.Conclusion:1.Chuanhu anti-gout mixture can significantly reduce the level of uric acid in gout patients,and reduce the inflammatory response by reducing CRP and ESR.2.Chuanhu anti-gout mixture mainly regulates purine metabolism and glycerol phospholipid metabolism.3.Chuanhu anti-gout mixture may reduce uric acid by up regulating the level of allopurinol. |
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