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
Objective: To explore the effect of hirudin on hyperuricemia rats and its mechanism. Methods: Male Wistar rats were randomly divided into control group, model group, allopurinol (30 mg/kg) group, hirudin low-, middle- and high-dose (0.2, 0.4, 0.8 g/kg) group. Rats were ig potassium oxonate (0.75 g/kg) to induce hyperglycemia model, once a day for five weeks. And all administration groups were respectively ig corresponding doses of drugs. The level of uric acid in serum and urine of rats were measured by biochemical method; The level of organic anion transporter 1 (OAT1) in kidney was measured by immunohistochemistry; The protein expressions of glucose transporter 9 (GLUT9), OAT1 and urate transporter 1 (URAT1) in kidney were measured by western blotting; The expression levels of GLUT9, OAT1 and URAT1 mRNA in kidney were detected by qRT-PCR. Results: Compared with control group, the level of uric acid in serum and urine of rats in model group was significantly increased (P < 0.01), the expressions of GLUT9, URAT1 mRNA and protein were significantly increased (P < 0.01), the expressions of OAT1 mRNA and protein were significantly decreased (P < 0.01). Compared with model group, the level of uric acid in serum and urine of rats in hirudin group were significantly decreased (P < 0.01), the expressions of GLUT9, URAT1 mRNA and protein were significantly reduced (P < 0.01), the expressions of OAT1 mRNA and protein were significantly increased (P < 0.01). Conclusion Hirudin can reduce the uric acid by regulating the expressions of renal urate transporters OAT1, URAT1 and GLUT9 in hyperuricemia rats.
ABSTRACT
Objective: To investigate the anti-gout effect of hirudin and its mechanism. Methods: Hypoxanthine was used to replicate mouse model of hyperuricemia. Sodium uric induced acute gouty inflammation in rats to observe the effect of hirudin on the level of uric acid and inflammation induced by acute hyperuricemia. The serum uric acid, serum urea nitrogen, serum xanthine oxidase activity, and liver xanthine oxidase activity were observed in chronic hyperuricemia mouse model induced by potassium oxonate. The changes of renal pathology, the level of C-reactive protein (CRP) and the expression of glucose transporter 9 (GLUT9) were also be tested. Results: Hirudin could significantly reduce the serum uric acid level in hyperuricemia mice induced by hypoxanthine and significantly inhibit acute toe swelling induced by sodium uric acid in rats. It could significantly reduce the level of serum hyperuricemia, decrease the level of blood urea nitrogen (BUN), significantly inhibit the expression of GLUT9 and alleviate the pathological changes of kidney in chronic hyperuricemia mice induced by potassium oxazinate. Conclusion: Hirudin has significant anti-hyperuricemia and anti-gout effects, and its mechanism may be related to the protection of kidney and the regulation of GLUT9 expression.
ABSTRACT
Sixty SD male rats were randomly divided into normal group, model group, benzbromarone group(20 mg•kg⁻¹•d⁻¹), chicory extract high dose, middle dose and low dose groups (5, 7.5, 10 g•kg⁻¹•d⁻¹). The rats in normal group were given with water, and the rats in other groups were given with 10% fructose solution to establish hyperuricemia models. All the rats were sacrificed on the 42th day. Then their serum uric acid(SUA), serum creatinine(CRE), urea nitrogen(BUN) and urinary uric acid(UUA) levels were detected to calculate the clearance rate of uric acid in kidney(CUA). Meanwhile, the protein and gene expression levels of renal glucose transporter family member 9(Glut9) were detected by immunohistochemical and Real-time quantitative reverse transcription-polymerase chain reaction(RT-qPCR) methods. The effects of Chinese herb chicory extract on expression of renal Glut9 and decreasing uric acid were explored in this study, and the results showed that chicory extract could reduce SUA level in rats with hyperuricemia, increase renal CUA, decrease the protein expression of renal Glut9, inhibit uric acid re-absorption in kidney, and thus promote renal uric acid excretion.
ABSTRACT
Aim To investigate the effects of 3 ,5 ,2 ’ , 4’-tetrahydroxychalcone (P40) on urate excretion, as well as mRNA and protein expressions of renal URAT1 and GLUT9 in hyperuricemic mice. Methods Sixty Kunming mice were randomly divided into six groups:normal control group, hyperuricemic group ( model group), P40 2. 0, 4. 0, 8. 0 mg·kg-1 groups and positive control group. All drugs were administered in-tragastrically to mice for 5 doses. Hyperuricemic mice were induced by intraperitoneal injection of uric acid (0. 15 g·kg-1 body weight) for 3 times. The urate levels were assayed with the phosphotungstic acid method. The mRNA and protein expressions of GLUT9 and URAT1 were determined by RT-PCR and Western blot. Results P40 at a dose of 4. 0 and 8. 0 mg · kg-1 significantly reduced the serum urate levels in a dose-dependent manner, when compared with untreat-ed hyperuricemic mice ( P<0. 05 or 0. 01 ) . The he-patic urate contents decreased in untreated-and treated-hyperuricemic mice as compared with normal mice ( P<0. 01 ) . Furthermore, P40 had no influence on the renal URAT1 mRNA and protein expression levels, while it could down-regulate renal GLUT9 protein ex-pression but not mRNA expression in hyperuricemic mice. Conclusion P40 possesses potent uricosuric effects associated with urate reabsorption by down-regu-lating the protein expression of GLUT9 in kidney.