ABSTRACT
With the improvement of people's living standard and the change of dietary structure, the prevalence of gout has increased gradually with the increased intake of protein, sugar and fat. There has been a positive correlation between gout and age, and the age of onset decreased gradually. The inflammation induced by sodium urate crystal is the pathological basis of gout, which activates innate immunity, releases many kinds of inflammatory mediators, such as interleukin(IL)-1β, IL-6 and tumor necrosis factor(TNF)-α, and then causes inflammatory cascade reaction and acute attacks, such as joint redness, swelling and heat pain. There is a spontaneous remission mechanism in gout. For one thing, macrophages reduce the stimulation of monosodium urate(MSU) through phagocytosis of MSU crystals as foreign bodies, for another, differentiated and mature macrophages secrete anti-inflammatory factor transforming growth factor(TGF)-β1, inhibit the expression of inflammatory factors and promote spontaneous relief of acute gout attack. In addition to the activation mechanism of intracellular signaling molecules associated with inflammatory response, the inflammatory mechanism of gout also involves complement activation, cell activation and other pathways. The complications caused by gout, such as cardiovascular system damage and joint destruction, are seriously harmful to human health. At present, western drugs, such as allopurinol and febuxostat, exert an effect in inhibiting xanthine oxidase. Benzimarone has effect in reducing renal absorption of uric acid and promoting uric acid excretion by inhibiting uric acid transporter 1(URAT1) and glucose transporter 9(GLUT9). Even Lesinurad and other medicines in current studies are based on the inhibition of uric acid re-absorption, but with adverse reactions that limit the clinical application. The treatment of gout with traditional Chinese medicine(TCM) has multi-target characteristics, with advantages in reducing uric acid, resisting inflammation and improving joint function and a high safety. It has been gradually popularized and applied in clinical treatment of gout. Therefore, it is a promising research direction to treat gout with TCM and western medicine based on the pathomechanism of gout.
ABSTRACT
During the uric acid production, excretion and reabsorption in the liver, kidney and intestine, several uric acid transporter proteins are involved in these processes. A large number of studies have shown that glucose transporter 9 plays an important role in the uric acid transport in the liver, kidney and intestine, and participates in the uric acid reabsorption. The ATP-binding cassette superfamily G member 2 is mainly expressed in the apical membrane of the proximal tubular epithelial cells of the kidney, which is involved in the uric acid secretion. The multidrug resistant protein 4 is expressed in the apical membrane of the renal tubular epithelial cells, which transfers uric acid from the renal tubular epithelial cells into the renal tubular lumen. The urate-anion transporter 1 as well as the organic anion transporters 1 and 3 are all the organic anion transporters belonging to the SLC22 A family of transmembrane transporters, and all participate in the uric acid transport in the kidney, especially the uric acid secretion and excretion. In this review, we summarize the research progress of these uric acid transporters, focusing on their effects on the regulation of the serum uric acid balance.
ABSTRACT
[ ABSTRACT] AIM:To explore the effect of renal transporter glucose transporter 9 ( Glu9 ) on hyperuricemia in the rats induced by fructose.METHODS:SD male rats (n=30) were randomly divided into normal group, model group and benzbromarone group , according to the weight .The rats in normal group was given water , while the rats in model group and benzbromarone group were given 10%fructose solution to establish hyperuricemia model .At the same time , the rats in normal group and model group were given a gavage of distilled water , while the rats in benzbromarone group were given benzbromarone at the dose of 20 mg/kg.The rats were sacrificed on the 40th day.The serum uric acid (SUA) and urinary uric acid (UUA) were detected to calculate the clearance rate of uric acid (CUA) in the kidney.The activity of hepatic xanthine oxidase ( XOD) was also measured .The expression of renal Glut 9 at mRNA and protein levels was determined by RT-qPCR and immunohistochemical staining .RESULTS:From the 20th day to the 40th day, the SUA in model group was significantly higher than that in normal group , but the UUA and CUA had no difference .On the 20th day, the SUA in benzbromarone group was markedly decreased as compared with model group , but UUA and CUA had no significant differ-ence.On the 40th day, the hepatic XOD activity in model group was significantly elevated , and no difference of XOD be-tween model group and the benzbromarone group was observed .Compared with normal group , the protein expression of Glut9 in the renal tissues of model group were markedly increased , and that in benzbromarone group was significantly lower than that in model group .However, no difference of the Glut9 mRNA expression was observed among groups .CONCLU-SION:Fructose drinking induces hyperuricemia in rats , which is probably related to the up-regulation of renal Glut9 ex-pression at protein level , and the increase in the reabsorption of uric acid in the kidneys .
ABSTRACT
<p><b>OBJECTIVE</b>To explore the effect of Compound Tufuling Granules ([characters: see text], CTG) on regulating glucose transporter 9 (GLUT9) expression in the kidney to influence the uric acid excretion by the kidney and serum uric acid (SUA) level in hyperuricemia mice.</p><p><b>METHODS</b>Sixty Kunming male mice were randomly divided into the control group, model group, benzbromarone group, and CTG high-, middle- and low-dose groups. The yeast extract and uricase inhibition method were used to build hyperuricemia model, and the corresponding drugs were administrated on the 7th day. On the 21st day the 24-h urine was collected, on the 22nd day the blood was collected, the SUA level was detected by uricase colorimetry, and the mRNA and protein expressions of GLUT9 were detected by quantitative real-time polymerase chain reaction and Western blot, respectively.</p><p><b>RESULTS</b>Compared with the model group, the levels of SUA and the mRNA and protein expressions of GLUT9 were significantly decreased, and the fraction excretion of uric acid (FEUA) was significantly increased in the CTG groups and benzbromarone group (all P<0.05). There was no significant difference in the above indicators between the CTG high-dose group and benzbromarone group (P>0.05). SUA is positively related to the GLUT9 mRNA and protein expressions in the kidney (P<0.05 or P<0.01).</p><p><b>CONCLUSIONS</b>CTG can significantly reduce the SUA and increase the FEUA. In addition, CTG can effectively inhibit the mRNA and protein expressions of GLUT9 in the kidney of hyperuricemia mice to inhibit the uric acid re-absorption, promote uric acid excretion and reduce SUA.</p>
Subject(s)
Animals , Male , Mice , Blotting, Western , Drugs, Chinese Herbal , Pharmacology , Glucose Transport Proteins, Facilitative , Hyperuricemia , Blood , Kidney , Chemistry , Real-Time Polymerase Chain Reaction , Uric Acid , BloodABSTRACT
A possible association between the polymorphism of glucose transporter 9 (GLUT9) rs1 3137343 and hyperuricemia was investigated in Chinese male population and the calculated genotype frequencies and allelic frequencies by PCR method and direct sequencing were reported.Data showed that there was statistical difference in GLUT9 rs13137343 genotype frequencies between hyperuricemia cases and controls(x2 =7.024,P =0.030).