【Animal Modeling】-Effect and mechanism of oltipraz in improving pain and inflammation in a mouse model of acute gouty arthritis

  Objective To establish a mouse model of acute gouty arthritis (AGA), and to observe and study whether Oltipraz can improve joint inflammation and pain in the model mice.

  Methods Healthy C57/BL6 male mice were randomly divided into control group (Control), model + solvent group (MSU + Veh), model + high-dose oltipraz group (MSU + 100 mg / kg Oltipraz), model + Oltipraz Tipraz low-dose group (MSU+30 mg/kg Oltipraz) and model+indomethacin group (MSU+10 mg/kg Indo). Except for the control group, which was injected with phosphate buffered saline, the mice in the other groups were injected with sodium urate (MSU) in the right ankle joint to prepare the AGA mouse model. Before and after the model was successfully prepared, the mice in the model + oltipraz group were intraperitoneally injected with oltipraz, the model + indomethacin group was intraperitoneally injected with indomethacin at the same time point, and the other groups were intraperitoneally injected with the same amount of solvent. Vernier calipers were used to measure the degree of ankle swelling in five groups of mice before and after modeling; 50% mechanical foot withdrawal response threshold (50% PWT) was detected by von Frey silk; pathological analysis of ankle synovial tissue sections; DigiGait imaging system The gait of mice was detected, and the changes of gait behavior before and after modeling were analyzed; oxidative molecular detection kit was used to detect the oxidative stress response of mouse ankle joint; qPCR technology was used to detect the expression of inflammatory factors in ankle joint tissue.

  Results Compared with the control group, the ankle joints of the mice in the model group were significantly swollen, and the 50% PWT was significantly reduced (P < 0.01). Pathology showed that the synovial tissue of the ankle joint of the mice in the model group had obvious inflammatory cell infiltration compared with the control group (P < 0.05). The gait analysis showed that the stride length of the model group was significantly shorter than that of the control group, and the paw contact area was significantly reduced (P < 0.01). Compared with the model + solvent group, the 50% PWT of the affected side of the mice in the model + 100 mg/kg oltipraz group was significantly increased (P < 0. 01); the degree of ankle swelling was significantly reduced; gait-related parameters were significantly improved (P < 0. 05); the level of oxidative stress in ankle joint tissue decreased significantly (P < 0. 05); the expression levels of inflammatory factors IL-1β and TNF-α also decreased significantly (P < 0. 01), Its effect is similar to indomethacin, but 30 mg/kg has no obvious effect.

  Conclusion Oltipraz can relieve ankle swelling and joint pain in AGA model mice, and this therapeutic effect is probably related to reducing the level of oxidative stress in the ankle joint tissue of AGA mice, increasing the expression of antioxidant substances and reducing the expression of inflammatory factors.