Abstract
ObjectiveGout is characterized by inflammatory arthritis with hyperuricaemia and deposition of monosodium urate (MSU) crystals in the joints. Several animal models have been proposed based on MSU crystals injection or high-fat diet feeding; however, neither hyperuricaemia model nor acute gout model can effectively reflect clinical features of gout. This study aimed to assess the effectiveness of a compound gout model induced by the combination of MSU crystals injection and high-fat diet feeding.MethodsThe compound gout model was induced by high-fat diet feeding per day and the intraplantar injection of MSU crystals (1 mg) into the footpad of each mouse every 10 days. Serum uric acid, foot swelling and pain analyses were performed at days 22, 32 and 42. Gout inflammation, serum proinflammatory cytokines and gut microbiota analyses were performed only at day 42.ResultsCompared to hyperuricaemia model or acute gout model, the compound gout model showed little advantages of elevating serum uric acid, causing foot swelling and gout inflammation, while it caused more severe serum inflammation and gut microbiota dysbiosis. Severe serum inflammation in the compound gout model could be reflected by the increased levels of IL-1α, IL-4, IL-6, IL-10, IL-12p40, IL-12p70, IFN-γ, KC, MCP-1 and MIP-1β. In addition, the compound gout model induced more alterations in the gut microbiota, including increasing levels of Desulfovibrio and Parasutterella.ConclusionThe injection of MSU and feed of high-fat diet have a combined effect on elevating serum inflammation and causing gut microbiota disorders in the process of establishing a gout model.
Highlights
Gout is a widespread metabolic disorder and it is characterized by the elevation of uric acid levels in the blood, leading to the deposition of monosodium urate (MSU) crystals in joints and soft tissues [1, 2]
Purine metabolic disorder can cause the elevation of uric acid, but enzymes uricase in most experimental animals can degrade uric acid which leads to the failure of establishing a stable hyperuricaemia model
After 7 days of acclimatization, all 28 mice were randomly divided into four groups: (1) control group (CT, n = 7 mice/group), fed normal diet and injected with PBS solution; (2) hyperuricaemia model group (HFD, n = 7 mice/group), fed high-fat diet (10% yeast extract) and injected with PBS solution; (3) acute gout model (MSU, n = 7 mice/ group), fed normal diet and injected with monosodium urate crystal (MSU) crystals (1 mg MSU crystals in 40 μL PBS/mouse every 10 days); (4) compound gout model (CGM, n = 7 mice/group), fed high-fat diet (10% yeast extract) and injected with monosodium urate crystal (MSU) crystals (1 mg MSU crystals in 40 μL PBS/mouse every 10 days)
Summary
Gout is a widespread metabolic disorder and it is characterized by the elevation of uric acid levels in the blood, leading to the deposition of monosodium urate (MSU) crystals in joints and soft tissues [1, 2]. The acute gout model can not reflect the pathogenesis of gout involving the urate deposition caused by purine metabolic disorder or gout-related recurrent episodes. Hyperuricaemia model is a purine metabolic disorder model caused by high-fat diet or an uricase inhibitor. Purine metabolic disorder can cause the elevation of uric acid, but enzymes uricase in most experimental animals can degrade uric acid which leads to the failure of establishing a stable hyperuricaemia model. There is still a lack of a suitable and reliable experimental animal model of gout
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