The Establishment Of Mouse Gout Model And The Attenuation Of Gout By Resveratrol In Mouse

Background and PurposeGout is a group of diseases resulted from purine metabolic disorder and (or) uric acid excretion disorder which can lead to elevated blood uric acid, with the characteristics of MSU crystals in joint synovial fluid and other tissues. Repeated episodes of acute inflammation, chronic gout stone formation and bone erosion are the main clinical manifestations of gouty arthritis, whose pathological basis is hyperuricemia. The present studies consider that MSU crystals activating inflammation by identifying toll-like receptors on the cell surface and activating NF-κB、AP-1signaling pathways is the main mechanism of gouty arthritis. MSU crystals can also activate the NALP3inflammation complex and eventually led to the release of mature IL-1β. Therefore reducing the level of blood uric acid and inhibiting inflammatory pathways may be the effective measures for prevention and treatment of gout attacks.Recent studies found that silence adjusting factor1(Sirtl) could inhibit the transcription activity of NF-κB and AP-1, lower the expression of various inflammation related factors, and thus alleviate inflammation. In addition, the Sirtl can also regulate cell metabolism and function, participating in metabolic diseases such as diabetes and high cholesterol. Resveratrol (Res) is a kind of polyphenols natural phytoalexin and an agonist of Sirtl.This article observes the role of resveratrol in gout and hyperuricemia by establishing sustained mouse hyperuricemia models and mouse arthritis model induced by MSU, and using Sirtl agonist resveratrol intervening the two models.Content and Methods First establish sustained hyperuricemia model and analysis the effect of resveratrol on hyperuricemia. Feeding6-week-age male Kunming mice with25%yeast extract feed combined with intraperitoneal injection of250mg/kg potassium oxonic once a day for3weeks to establish hyperuricemia model. Treatment group at the same time of modeling were intragastric administrate20mg/kg resveratrol once a day, analysis serum uric acid and creatinine of different time and detect renal pathological changes by HE staining method.Second, induce mice acute arthritis with MSU crystal and detect the role of resveratrol on the arthritis model. Injecte MSU in six to eight weeks old male C57BL/6mice’s right food to induce acute gouty arthritis model, assess joint inflammation by evaluating the degree of joint swelling by measuring the thickness of food in digital display caliper and testing99mTc absorption. Give different doses of resveratrol for interventional treatment at different time to assess the variation of joint inflammation.ResultsYeast combined with oxonic potassium can establish sustained stable hyperuricemia model with significant rise of serum uric acid and no severe renal damage during3to14days of modeling. Whereas, at the21st day, uric acid level rise slow, creatinine mild rise, and the kedney HE staining shows that glomerulus capsule wall thickening, renal interstitial inflammatory cell infiltration and renal tubular epithelial cell swelling. Treatment group was simultaneously given resveratrol when inducing hyperuricemia model, the result is that compared with the model group, blood uric acid level in mice of intervention group significantly decreased during the same period (P<0.05), and the kidney injure improved.Local injection of MSU crystals in mice feet can induce mice acute arthritis and the degree of inflammation is positively associated with the level of MSU, meanwhile the inflammation has time limiting with most notable inflammation in8-12hours after MSU injection and gradual reduction after24hours. With resveratrol pretreatment, arthritis induced by MSU crystal is ameliorative compared with the unpretreatment group (P<0.05). Resveratrol was respectively pretreated for3days,7days,14days and then MSU crystal was used to induce inflammation, the result is that the inflammation is most ameliorative in14days resveratrol pretreatment group and the effect is positively related with the dose of resveratrol.Conclusion1. Combination of yeast and potassium oxonic can establish sustained stable hyperuricemia model.2. Sirtl agonist resveratrol can prevent and treat gout attacks by its functions of improve hyperuricemia and ameliorate inflammation.