| OBJECTIVE: To investigate the relationship between life events and serum uric acid levels in patients with hyperuricemia.To analyze the relationship between chronic stress hormones(catecholamines and glucocorticoids)and serum uric acid levels.What's more,explore the molecular mechanism of the increasing of uric acid nduced by the stress hormone.METHODS:(1)Clinical research: Using life events scale to qualitatively and quantitatively analyze 60 case of hyperuricemia patients.And compare the general data and biochemical indicators of patients with hyperuricemia under different pressures,by measuring blood pressure,blood lipids,liver function and so on.Conducting multiple regression for further correlation analysis.In addition,the levels of cortisol was measured by enzyme-linked immunosorbent assay to analyze the relationship between chronic stress hormones and serum uric acid.(2)Basic research: A chronic stress model was established on the UOX-KO spontaneous hyperuricemia Wistar rat model to detect blood uric acid and related stress hormone levels.Epinephrine and dexamethasone were treated in HepG2 cells to observe the association between hormones and uric acid.Western blot and other methods were used to detect the expression of xanthine oxidoreductase-related molecules in liver and HepG2 cells under different treatment conditions.RESULTS: Clinical studies:(1)Patients with a total score of 20 or less on the life event scale were included in the low-pressure group,and the total score was greater than 20 points in the high-pressure group.The highest frequency of positive and negative life events are outstanding achievement and stress in work and study.(2)The frequency of gout attacks and cholesterol,triglyceride,serum creatinine,serum uric acid,and cortisol levels in the high-pressure group were significantly higher than those in the low-pressure group.(3)The positive life event stimulation was positively correlated with cholesterol and triglyceride,and the negative life event stimulation was positively correlated with uric acid.In the multiple linear regression analysis with serum uric acid as the dependentvariable,the frequency of gout attacks and the stress group finally entered the regression model in the last year.(4)In the multiple linear regression analysis with blood uric acid as the dependent variable,the frequency and pressure group of gout attacks in the last year were independently correlated with blood uric acid levels.Basic research:(1)The weight and weight gain of UOX-KO rats in the stress group were lower than those in the control group.Compared with the control group,serum hormone levels,serum uric acid and serum lipids in the stress group UOX-KO rats increased.Liver lipid deposition was reduced in the stress group UOX-KO rats,and white fat in the abdomen was reduced.The expression and activity of xanthine oxidase in the liver of UOX-KO rats in the stress group increased.(2)The levels of uric acid and xanthine oxidase in HepG2 cells treated with stress hormones(adrenalin and dexamethasone)increased.Epinephrine activates XOR via the p38MAPK/C/EBP?pathway.CONCLUSION:In patients with hyperuricemia who are greatly stimulated in family life and work in life events,mental stress can cause elevated levels of cholesterol,triglycerides and serum uric acid,and elevated triglycerides and cholesterol.It is related to positive life events,and the rise of blood uric acid is related to negative life events.For patients with hyperuricemia,high-stress and frequent gouts are associated with higher levels of serum uric acid.In the in vivo study of basic research,the levels of stress hormones(adrenalin and glucocorticoid)in rats with hyperuricemia under chronic stress were increased,and XOR in liver and adipose tissue were activated with the increasing of uric acid levels.In adipocytes,this phenomenon may be due to adrenaline acting on the surface of adipocytes?3-AR,activation of XOR via the p38MAPK/C/EBP?pathway,and XOR activity feedback enhancement in order to inhibit lipolysis caused by adrenaline.In hepatocytes,in addition to the enhanced feedback of XOR activity,it may be due to the lipolysis effect in fat and liver,and elevated blood lipids are taken up into the liver,resulting in hyper-synthesis of neutral fat synthesis and the regeneration of uric acid from5-phosphoriribose. |
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