2.6. Animal Model of Acute Gouty Arthritis with Hyperuricemia in Rats and Experimental Design

After a 7-day acclimatization period, an experimental animal model of hyperuricemia was induced using potassium oxonate (uricase inhibitor). Briefly, potassium oxonate (1.5 g/kg/day) dissolved in distilled water was orally administered to 70 rats; the dosing volume was 1 mL/100 g body weight, once daily for 21 consecutive days. In addition, 10 rats were used to form the normal control group (administration of distilled water only). Blood samples were collected from the eyelids of model rats at weeks 1, 2, and 3, and the levels of uric acid in the serum were measured. Rats with blood uric acid levels >110 μmol/L at week 3 indicated that the model was successfully induced. Animals with high or low levels of uric acid in the blood were removed, and 50 rats were selected for the subsequent experiment.

The successfully established hyperuricemia model rats were randomly divided into six groups (n = 10 per group): model control, normal control, colchicine, and TTC high dose (TTC-H), TTC medium dose (TTC-M), and TTC low dose (TTC-L). All rats were anesthetized with 2.5% isoflurane, followed by injection of 50 μL MSU crystals (25 mg/mL) or normal saline into the medial side of the right tibiotarsal joint (ankle) of each rat to further establish the model of acute gouty arthritis with hyperuricemia. Of note, the contralateral bulging of the joint capsule was the standard for drug injection [28]. After the administration of MSU, each group intragastrically received TTC or colchicine once daily for 7 days. The normal control group and the model control group were treated with PBS (Figure 1).

Experimental design. A hyperuricemia model was established during the first 3 weeks through the daily administration of potassium oxonate. Subsequently, a model of acute gouty arthritis with hyperuricemia was established via injection of MSU crystals, as described in the Materials and Methods section. This was followed by the administration of TTC, colchicine, or PBS (control) once daily for 7 days. The degree of ankle swelling, inflammation index, and dysfunction index were assessed at 12, 24, 48, 72, and 96 h after the injection of MSU crystals. Rats were sacrificed to test for proinflammatory cytokines, renal and liver function, lipid profile, and histological analyses.