Effects of Tongfengning（痛风宁） on Intestinal Flora and Intestinal Uric Acid Metabolism in Model Mice of Hyperuri⁃cemia of Spleen Deficiency with Exuberance of Dampness Syndrome / 中医杂志

ObjectiveTo explore the possible mechanisms of Tongfengning （痛风宁， TFN） in treating hyperuricemia （HUA） of spleen deficiency with exuberance of dampness syndrome. MethodsTen of 60 mice were randomly selected， and were fed with regular diet as the control group， while the remaining 50 mice were fed with high-fat and high-sugar diet combined with excessive exercise and potassium oxonate-allopurinol suspension to establish an HUA animal model of syndrome of spleen deficiency with exuberance of dampness. After the successful modeling， in order to better observe the effects of TFN on the intestinal microbiota of the model mice， a mixed antibiotic suspension was administered by gavage to induce further dysbiosis of the intestinal microbiota in the model mice. Fifty sucessfully modeled mice were randomly divided into model group， TFN group， allopurinol group， probiotics group， and an allopurinol + probiotics group， 10 in each group. The TFN group was administered TFN liquid at a dosage of 19.11 g/（kg·d） by gavage. The allopurinol group was administered allopurinol suspension at a dosage of 78 mg/（kg·d） by gavage. The probiotics group was administered live combined Bifidobacterium and Lactobacillus tablets suspension at a dosage of 3 g/（kg·d） by gavage. The allopurinol + probiotics group was administered allopurinol at a dosage of 78 mg/（kg·d） and live combined Bifidobacterium and Lactobacillus tablets suspension at a dosage of 3 g/（kg·d） by gavage. The control group and model group were administered normal saline at a dosage of 19.11 ml/（kg·d） by gavage. The interventions were continued for 21 days. In order to maintain a stable high blood uric acid state， all groups but the control group continued modeling while receiving drug intervention. The changes in spleen deficiency syndrome scores， blood uric acid levels， microbial community structure， acetic acid and butyric acid content in intestinal lavage fluid， adenosine deaminase （ADA） and xanthine oxidase （XOD） content in small intestine tissue， as well as ATP-binding cassette transporter G2 （ABCG2）， glucose transporter 9 （GLUT9） protein and mRNA expression in the small intestine tissue were compared among the groups of mice. ResultsCompared with the control group， the model group showed increased spleen deficiency syndrome scores， blood uric acid levels， relative abundance of phylum Firmicutes， Firmicutes/Bacteroidetes ratio， abundance of Bacteroides genus， Klebsiella genus， and Enterococcus genus， acetic acid content in intestinal lavage fluid， ADA and XOD content in small intestine tissue， as well as GLUT9 protein and mRNA expression （P<0.05）. The number of operational taxonomic units （OTUs） of intestinal microbiota， relative abundance of Bacteroidetes phylum， abundance of Lactobacillus genus and uncultured Bacteroides genus， butyric acid content in intestinal lavage fluid， and ABCG2 protein and mRNA expression in small intestine tissue were significantly decreased （P＜0.05）. Compared with the model group， in the group treated with TFN， probiotics， and allopurinol + probiotics， the spleen deficiency syndrome score， blood uric acid level， relative abundance of Firmicutes， acetic acid content in intestinal lavage fluid， ADA and XOD content in small intestine tissue， GLUT9 protein and mRNA expression significantly decreased. The number of gut microbiota OTUs， relative abundance of proteobacteria， butyric acid content in intestinal lavage fluid， ABCG2 protein and mRNA expression in small intestine tissue significantly increased （P＜0.05）. In the probiotics group， the ratio of Firmicutes to Bacteroidetes decreased. In the TFN group， the abundance of Lactobacillus and uncultured Bacteroidetes significantly increased， while the abundance of Parabacteroides， Klebsiella， and Enterococcus significantly decreased （P＜0.05）. Compared with the TFN group， allopurinol group and the probiotics group showed elevated blood uric acid levels， abundance of Bacteroidetes， ADA and XOD levels in intestinal tissue， and GLUT9 mRNA expression. The relative abundance of Firmicutes， abundance of lactobacilli， and ABCG2 mRNA expression significantly decreased. The probiotics group showed elevated GLUT9 protein expression in intestinal tissue. The probiotics group and the allopurinol plus probiotics group showed significantly higher scores for spleen deficiency syndrome in mice， and lower levels of butyric acid in mouse intestinal lavage fluid. The allopurinol group showed decreased numbers of OTUs in mouse intestinal flora， decreased abundance of proteobacteria， and butyric acid levels in intestinal lavage fluid. The allopurinol group also showed decreased ABCG2 protein expression in intestinal tissue， increased acetic acid levels in intestinal lavage fluid， increased abundance of Klebsiella， and significantly elevated GLUT9 protein expression （P＜0.05）. ConclusionsThe treatment of HUA with TFN may be associated with the regulation of intestinal probiotics （such as lactobacilli） and pathogenic bacteria （such as Klebsiella）， as well as the production of bacterial metabolites such as acetic acid and butyric acid. It may also involve reducing the expression of ADA and XOD in the intestines， decreasing intestinal uric acid production， upregulating the expression of intestinal epithelial urate transporter ABCG2， downregulating GLUT9 expression， and promoting intestinal uric acid excretion. These factors are related to the syndrome of spleen deficiency with exuberance of dampness.

Serum Uric Acid Levels are Associated with Cardiometabolic Risk Factors in Healthy Young and Middle-Aged Adults / Os Níveis Séricos de Ácido Úrico estão Associados a Fatores de Risco Cardiometabólico em Adultos Jovens e de Meia-Idade Saudáveis

Abstract Background: Observational studies have highlighted an association between serum uric acid (SUA) levels and cardiovascular risk factors. Despite the growing body of evidences, several studies were conducted in older individuals or in carriers of diseases susceptible to affect SUA levels and cardiometabolic risk markers. Objective: To evaluate the relationship of SUA with body adiposity, metabolic profile, oxidative stress, inflammatory biomarkers, blood pressure and endothelial function in healthy young and middle-aged adults. Methods: 149 Brazilian adults aged 20-55 years, both sexes, underwent evaluation of body adiposity, SUA, fasting glucose and insulin, lipid profile, malondialdehyde (MDA), high sensitivity C-reactive protein (hs-CRP), adiponectin, blood pressure and endothelial function. Endothelial function was assessed by the reactive hyperemia index (RHI) derived from peripheral arterial tonometry method. Participants were allocated in two groups according to SUA levels: control group (CG; n = 130; men ≤ 7 mg/dL, women ≤ 6 mg/dL) and hyperuricemia group (HG; n = 19; men > 7 mg/dL, women > 6 mg/dL). A P-value < 0.05 was considered statistically significant. Results: After adjustment for confounders, participants in HG compared with those in CG displayed higher body mass index (BMI): 34.15(33.36-37.19) vs.31.80 (26.26-34.42) kg/m2,p = 0.008, higher MDA: 4.67(4.03-5.30) vs. 3.53(3.10-4.07) ng/mL, p < 0.0001 and lower RHI: 1.68 ± 0.30 vs. 2.05 ± 0.46, p = 0.03). In correlation analysis adjusted for confounders, SUA was positively associated (p < 0.05) with BMI, waist circumference, LDL-cholesterol, triglycerides and MDA, and negatively associated (p < 0.05) with HDL-cholesterol, adiponectin and RHI. Conclusions: This study suggests that in healthy young and middle-aged adults higher SUA levels are associated with higher body adiposity, unfavorable lipid and inflammatory phenotype, higher oxidative stress and impaired endothelial function.

Resumo Fundamento: Estudos observacionais têm destacado uma associação entre níveis de ácido úrico sérico (AUS) e fatores de risco cardiovascular. Apesar do crescente conjunto de evidências, vários estudos foram realizados em indivíduos mais velhos ou em portadores de doenças passíveis de influenciar os níveis de AUS e marcadores de risco cardiometabólico. Objetivo: Avaliar a relação do AUS com adiposidade corporal, perfil metabólico, estresse oxidativo, biomarcadores de inflamação, pressão arterial e função endotelial em adultos jovens e de meia-idade saudáveis. Métodos: 149 adultos, brasileiros, com idades entre 20 e 55 anos, de ambos os sexos, foram submetidos a avaliação de adiposidade corporal, AUS, glicose e insulina de jejum, perfil lipídico, malondialdeído (MDA), proteína C-reativa ultra-sensível (PCR-us), adiponectina, pressão arterial e função endotelial. A função endotelial foi avaliada pelo índice de hiperemia reativa (RHI) derivado do método de tonometria arterial periférica. Os participantes foram divididos em dois grupos de acordo com os níveis de AUS: grupo de controle (GC; n = 130; homens ≤ 7 mg/dL, mulheres ≤ 6mg/dL) e grupo de hiperuricemia (GH; n = 19; homens > 7mg/dL, mulheres > 6mg/dL). Valor de p < 0,05 foi considerado estatisticamente significativo. Resultados: Após ajuste para fatores de confundimento, os participantes do GH comparados aos do GC apresentaram índice de massa corporal (IMC) mais alto: 34,15 (33,36-37,19) vs. 31,80 (26,26-34,42) kg/m2, p = 0,008, MDA mais alto: 4,67(4,03-5,30) vs. 3,53(3,10-4,07) ng/mL, p < 0,0001 e RHI mais baixo: 1,68 ± 0,30 vs. 2,05 ± 0,46, p = 0,03. Na análise de correlação ajustada para fatores de confundimento, o AUS se associou positivamente (p < 0,05) com IMC, circunferência da cintura, LDL colesterol, triglicérides e MDA, e se associou negativamente (p < 0,05) com HDL colesterol, adiponectina e RHI. Conclusões: Este estudo sugere que, em adultos jovens e de meia-idade saudáveis, níveis mais altos de AUS estão associados a maior adiposidade corporal, fenótipo inflamatório e de lipídios desfavorável, maior estresse oxidativo e função endotelial comprometida.

Effect of Qinqinye on Hyperuricemia Uric Acid Metabolism and Related Enzymes Activity / 中国中医药信息杂志

0.05). Positive medicine group, Qingqinye high dosage group, Qingqinye low dosage group and Qingqinye middle dosage group reduced blood ADA activity and better than model group (P