SAT0409 P2X7R PROMOTE THE ATTACK OF ACUTE GOUTY ARTHRITIS IN RATS FROM CLINICAL TO PATHOLOGY
Authors: Xiaojuan Dai, LI Xiangpei, Jinhui Tao, Xuan Fang, Yuan Xia, LI Xiaomei
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> ATP may be the second causative signal for the onset of gout, which acts on P2X7R to regulate the development of acute gouty arthritis (1). P2X7R is the most relevant to the inflammatory response in the P2X family and is also an ATP-gated cation channel (2) <h3>Objectives:</h3> The aim of this study was to activate P2X7R signaling pathway through changes in extracellular ATP concentrations, leading to the development of acute gouty arthritis and the production of pro-inflammatory. <h3>Methods:</h3> 120 male Sprague-Dawley rats were randomly divided into 3 groups: After establishment of acute gouty arthritis model, rats were given P2X7R agonist ATP, P2X7R inhibitor BBG and PBS, respectively. The clinical manifestations of the ankle joints were evaluated at 6h, 12h, 24h, 48h and 72h before the rats were sacrificed, and rat ankle synovial slices for H&amp;E staining. IL-1β, IL-6 and TNF-α in the serum of rats were detected by ELISA kits. <h3>Results:</h3> <b>1. P2X</b><b>7R regulates the development of acute gouty arthritis:</b> At 12h, the clinical scores of ATP group were significantly higher than those of BBG group and control group (P=0.001,0.042), and the control group was higher than BBG group (P=0.034); At 12h and 24h, the swelling index of ATP group was the most obvious than other two groups (P=0.000, 0.001; P=0.000, 0.003), followed by control group (P=0.009, 0.001); Furthermore, there was a large infiltration of inflammatory cells in the synovial tissue of the right ankle joint of rats, at 12h, and 24h, the infiltration of mononuclear cell in ATP group was significantly higher than that in BBG group and control group (P=0.000, 0.007; P=0.000, 0.001); The neutrophils infiltration in ATP group was the highest among the three groups at 24h (P=0.001, 0.04), and the control group was higher than BBG group (P=0.04). <b>2. P2X</b><b>7R regulates pro-inflammatory cytokines production:</b> At 24h, the level of IL-1β in ATP group was significantly higher than BBG group and control group (P=0.001, 0.003); At 6h, 12h and 24h, higher level of IL-6 in ATP group compared with BBG group and control group (P=0.004, 0.04; P=0.000, 0.002; P=0.001, 0.012); The level of TNF-α was obviously higher in ATP group than in BBG group and control group at 6h and 24h (P=0.007, 0.011; P=0.001, 0.018), and BBG group was lower than control group, but without statistically significant (P&gt;0.05). <h3>Conclusion:</h3> Activation of P2X7R can significantly promote the attack of acute gouty arthritis and the production of IL-1β, IL-6 and TNF-α, suggesting that P2X7R affects the development of acute gouty arthritis and regulates the secretion of pro-inflammatory cytokines. <h3>Reference</h3> [1] Tao JH, Zhang Y, Li XP. P2X7R: a potential key regulator of acute gouty arthritis. Semin Arthritis Rheum, 2013, 43(3): 376-380. (2) Hechler B, Gachet C. Purinergic receptors in thrombosis and inflammation[J]. Arterioscler Thromb Vasc Biol, 2015, 35:2307-2315 <h3>Disclosure of Interests:</h3> None declared