Combined effects of MSU crystals injection and high fat-diet feeding on the establishment of a gout model in C57BL/6 mice

Abstract Objective: Gout 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. Methods: The 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. Results: Compared 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-1 α, 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. Conclusion: The 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.(AU)

Effects of mesalamine on the expression of TNF-α, IL-6, IL-17 and intestinal barrier function with ulcerative colitis / 中国生化药物杂志

Objective To investigate the effect of mesalazine on the expression of TNF-α, IL-6, IL-17 and intestinal barrier function in patients with ulcerative colitis. Methods 76 patients with UC from January 2015 to April 2016 in The Fifth Central Hospital of Tianjin were collected and randomly divided into control group and observation group with 38 cases in each group. After admission were given maintenance of water and electrolyte, basic acid-base balance and nutritional support treatment, and the control group were treated with conventional drug sulfasalazine (SASP) treatment, two tablets each time, four times once day, four weeks for each course, the observation group was treated with mesalazine, four tablets each time, three times once day, four weeks each course of treatment. The levels of TNF-α, IL-6, IL-17, L/M and Baron endoscopic scores in the two groups were observed after two courses of treatment. The efficacy and side effects of the two groups were compared. Results No dropout or dropout cases in this study, two groups after the treatment of TNF-α, IL-6, IL-17, L/M, Baron scores were significantly decreased (P<0.05), but the observation group after treatment the above indexes were all significantly lower than the control group (P<0.05), the total effective rate of the observation group was 89.47%(34/38) higher than that of the control group 71.05%(21/38), the adverse reaction rate of 13.16% (5/38) was lower than that in the control group 34.21% (13/38), the differences were statistically significant(P<0.05). Conclusion Compared with conventional drug SASP, the effect of on the expression of TNF-α, IL-6 and IL-17 in serum of patients with UC and the improvement of intestinal barrier function can be effectively suppressed, which has the advantages of clinical efficacy and low adverse reaction rate.