慢性肾病合并高尿血酸症的评估与治疗

肾脏是尿酸排泄的重要器官，慢性肾脏病患者存在肾小球、肾小管以及肾血管损害，可引起肾脏尿酸排泄下降，导致血尿酸水平增高。而高尿酸血症是慢性肾脏病发生、发展，以及导致心血管事件和死亡的危险因素，因此高尿酸血症与肾脏疾病互为因果、互相加重。

Relationship between hyperuricemia and metabolic syndrome

Objective: To investigate the relationship between metabolic syndrome and hyperuricemia. Methods: A total of 2 374 subjects who received health examination in our hospital from Jan. 2004 to Dec. 2006 were enrolled in our study. Hyperuricemia is defined as ≥7 mg/dl (in men) or ≥6.0 mg/dl (in women). Metabolic syndrome was defined using AHA/NHLBI (American Heart Association/National Heart, Lung, and Blood Institute) criteria. Results: (1) The overall prevalence of hyperuricemia was 13.10%. The condition was more common in men than in women (19.07% vs 3.42%). (2) Among men, uric acid concentration is statistically significantly positively correlated with waist circumference, blood pressure, and triglyceride. Uric acid is negatively correlated with serum high-density lipoprotein-cholesterol (HDL-C). Uric acid concentration is most strongly correlated with serum triglyceride (r=0.379) and waist circumference (r=0.297). Among women, statistically significant positive correlations were noted for the serum uric acid concentrations with waist circumference, triglyceride and fasting plasma glucose. Serum triglyceride (r=0.329) and waist circumference (r=0.234) are most strongly correlated with uric acid concentrations. (3) Men with hyperuricemia had a 1.634-fold increased risk of metabolic syndrome as compared with those without hyperuricemia odds ratio (OR)=1.634, P=0.000. Women with hyperuricemia had a 1.626-fold increased risk of metabolic syndrome (OR=1.626, P=0.000) as compared with those without hyperuricemia. Conclusion: Hyperuricemia is prevalent among Chinese population. Additionally, serum uric acid is positively associated with metabolic syndrome.

Abdominal Fat Accumulation with Hyperuricemia and Hypercholesterolemia Quail Model Induced by High Fat Diet

Objective To establish abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model fed with high fat diet. And then to investigate the pathological characteristics of this quail model. Methods Thirty Longcheng quails were randomly divided into two groups： control group and model group （n=15）. The control group quails were fed with normal diet and model group quails were fed with high fat diet for 14 days. After a 12-hour overnight fast, liver and abdominal fat at euthanasia as well as serum were collected. The levels of serum uric acid, total cholesterol, high density lipoprotein cholesterol （HDL-C）, low density lipoprotein cholesterol （LDL-C）, triglyceride, free fatty acid （FFA）, and blood glucose were assayed. The activity changes of adenosine deaminase （ADA）, xanthine oxidase （XOD）, lipoprotein lipase （LPL）, hepatic lipase （HL）, and fatty acid synthetase （FAS） were analyzed. Results Compared with control group, the abdominal fat content （0.74±0.63 vs. 1.36±0.65 g, P〈0.05） and abdominal fat index （0.44%±0.30% vs. 0.85%±0.30%, P〈0.01） as well as live lipid index （3.61%±0.65% vs. 11.33%±2.14%, P〈0.01） in model group significantly increased; the levels of serum uric acid （210.61±94,76 vs. 304.25±141.94 /amol/L, P〈0.05）, total cholesterol （4.20±0.51 vs. 20.10±11.25 mmol/L, P〈0.01）, LDL-C （1.16±0.29 vs. 10.78±6.48 mmol/L, P〈0.01）, and FFA （0.39±0.14 vs. 0.55±0.15 mmol/L, P〈0.01） in model group significantly increased; HDL-C （5.85±0.95 vs. 4.14±2.03 mmol/L, P〈0.05） significantly decreased; the levels of triglyceride and blood glucose had no significant changes （P〉0.05）; the activities of ADA （9.71±3.05 vs. 17.19±5.10 U/ml, P〈0.01） and XOD （10.58±6,88 vs. 19.22＋9.44 U/L, P〈0.01） in model group significantly increased; and FAS, LPL, HL had no significant changes （P〉0.05）. Conclusions High fat diet can induce abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model. The changes of uric acid and lipid metabolic enzyme activities may he the pathological mechanism of abdominal fat accumulation with hyperuricemia and hypercholesterolemia.

The inhibitory effect of lotus leaf extract on hyperuricemia and its potential mechanism

Objective:Lotus leaf is a traditional Chinese herb that has been used successfully for centuries for relieving edema by inducing diuresis.Based on its good clinical evidence and anti-hypertensive effectiveness,this study aimed to investigate the potential mechanism of the hyperuricemic inhibitory effects of lotus leaf crude extract(LL)and lotus leaf total alkaloids fraction(LA).Methods:The xanthine oxidase(XOD)inhibitory effect of LL and LA was analyzed in vitro by determining mRNA expression and protein expression levels of hepatic XOD.The hyperuricemic inhibitory effect of the lotus leaf was analyzed in vivo in a potassium oxonate(PO)-induced rat model by determining mRNA expression for renal urate transporters.Results:At a concentration of 40mg/mL,LL and LA suppressed XOD enzymatic activity by 37.35%±9.50%and 47.73%±8.32%,respectively.Both LL and LA administration significantly reduced the concentration of uric acid in the serum and liver of PO-induced hyperuricemic rats.Both LL and LA administration could inhibit XOD mRNA and protein expression,activate renal organic anion transporter 1/3 mRNA expression,and inhibit renal urate reabsorption by decreasing renal GLUT9 and renal urate transporter 1.Conclusions:Insight was gained into the mechanism behind the hyperuricemic inhibitory effects of LL and LA.Our results suggest that they act on two targets:decreasing the production of uric acid by inhibiting mRNA and protein expression of XOD in the liver,and regulating the mRNA expression of renal urate transporters in the kidneys.

Effect of TongFengNing Decoction on Uric Acid Levels and Xanthine Oxidase Activity in Hyperuricemia Rats

Objective To observe the effect of TongFengNing Decoction （TD） on uric acid levels, xanthine oxidase （XOD） activity, and XOD mRNA expression of hyperuricemia （HUA） model rats. Methods： 90 rats were randomly divided into 6 groups （n=15）, and the HUA model in all groups except the blank group was established by administering hypoxanthine （HX） by gavage and injecting potassium oxonate （OAPS） intraperitoneally. Rats in all TD groups and allopurinol group were administered multiple doses of TD and a single dose of allopurinol by gavage twice daily for 21 days, while the blank group and the model group were administered normal saline. On the 7th, 14th, and 21st days of drug intervention, serum uric acid （SUA）, urine uric acid （UUA）, intestinal uric acid （IUA）, as well as XOD activity and mRNA expression in the liver and small intestine were measured in randomly selected 5 rats of each group. Results： On the 14th and 21st days of intervention, all TD dose groups and the allopurinol group showed decreased SUA and IUA levels, increased UUA levels, as well as decreased XOD activity and mRNA expression in the liver and small intestine, compared with the model group （P 〈 0.05）. The low- and high-dose TD group and the allopurinol group showed increased SUA and IUA levels, as well as XOD activity and mRNA expression in the liver and small intestine, and decreased UUA levels, compared with the moderate-dose TD group （P〈0.05）. Upon extending the drug intervention time of each TD dose group, SUA and IUA levels, XOD activity, and XOD mRNA expression in the liver and small intestine decreased and UUA levels increased （P 〈 0.05）. Conclusion： TD reduces SUA levels in HUA model rats, which promotes uric acid excretion and inhibits XOD activity and XOD mRNA expression to reduce uric acid production. The reduction in uric acid level by the intermediate dose of TD was better than that by allopurinol and the low and high doses of TD.

Safety and tolerability of available drugs for hyperuricemia:a critical review and an update on recent developments

Hyperuricemia(HUA)is a metabolic disease caused by excessive production of serum uric acid(s UA)or decreased excretion of s UA in the body.HUA is an independent risk factor for chronic kidney disease,hypertension,cardiovascular and cerebrovascular diseases,and diabetes mellitus.Timely and effective treatment for reducing s UA plays a key role in reducing urate deposition,preventing gout attacks,and reducing kidney damage and the occurrence of other accompanying diseases.Four pharmacological methods can be used to treat HUA:decrease urate production,increase urate excretion,prevent urate formation,and catabolize urate.To provide a reference for clinical treatment and new medical research for HUA,the drugs and potential drugs for HUA were reviewed in the present work.

Clinical observation on electroacupuncture plus Jiawei Jinhuanggao(Supplemented Golden Yellow Paste) for gouty arthritis

Objective： To observe the clinical effect of electroacupuncture（EA） plus self-made Jiawei Jinhuanggao（Supplemented Golden Yellow Paste） for gouty arthritis. Methods： A total of 80 cases with gouty arthritis were randomly allocated into an observation group（n=40） and a Western medication group（n=40）. Cases in the observation group received EA and external application of self-made Jiawei Jinhuanggao（Supplemented Golden Yellow Paste）, whereas cases in the Western medication group took Colchicine and Allopurinol tablets orally. After 10 d of treatment, the pain, joint swelling and uric acid in blood were observed. In addition, the follow-up was conducted 6 months after end of the treatment to evaluate the long-term effect. Results： After treatment, there were no between-group statistical differences in pain and uric acid in blood（P〈0.05）; and there were between-group statistical differences in joint swelling and relapse rate（P〈0.05）. The total effective rate was 97.5% in the observation group, versus 95.0% in the Western medication group, showing no statistical difference（P〈0.05）. Conclusion： EA plus Jiawei Jinhuanggao（Supplemented Golden Yellow Paste） has safe and long-term efficacy for gouty arthritis efficacy.

Relation of uric acid levels to aortic root dilatation in hypertensive patients with and without metabolic syndrome

Objective:Uric acid(UA) is considered to be a powerful predictor of cardiovascular risk and hyperuricemia might be involved in the metabolic syndrome(MS).This study aims to investigate the relation between UA levels and aortic root dilatation.Methods:A total of 348 hypertensive patients [age(67.5±9.8) years] with or without MS were included in the study.The aortic root diameters at the aortic annulus,the sinuses of Valsalva,the sinotubular junction,and the proximal part of the ascending aorta were measured using a two-dimensional(2D) echocardiography.Serum UA levels were also measured for all patients.Results:A high UA level is independently associated with aortic root diameters at the sinuses of Valsalva(P=0.001) and the proximal ascending aorta(P<0.0001) in the hypertensive patients without MS.In contrast,aortic root diameters were not significantly related to UA levels in the hypertensive patients with MS.Furthermore,increased UA levels were associated with an increased risk for aortic root dilatation in the patients without MS(sex-adjusted hazard ratio 1.75,95% confidence intervals(CI) 1.27-2.41),but not in those with MS.Conclusions:This study demonstrated an independent relationship between the aortic root dimensions and increased levels of serum UA in the hypertensive patients without MS.Further understanding of the mechanisms underlying these associations may allow a clearer interpretation of the potential value of specific urate-lowering treatment on cardiovascular disease.