Study On Change Of NLRP3 Inflammasome Signalling Pathway In Patients With Acute Gouty Arthritis

Objective: To study relevant molecular expression of NLRP3 inflammasome signalling pathway and its association with clinical manifestations in peripheral blood mononuclear cells (PBMC) from patients with acute gouty arthritis (AGA) and healthy individuals; to explore the role of NLRP3 inflammasome signalling pathway in the pathogenesis of AGA.Methods: (1) 24 acute gouty arthritis patients and 24 healthy individuals were enrolled into the study. The clinical data of acute gouty arthritis patients and healthy individuals were collected. PBMC were isolated from blood in vitro. (2) The NLRP3, ASC, caspase-1 and IL-1βmRNA of PBMC were measured using real-time quantitative polymerase chain reaction (RT-qPCR) in acute gouty arthritis patients and healthy individuals, and the differences of genes expression in two groups were compared using Students't-test was used in two independent samples and Pearson correlation was used to evaluated relationship between mRNA level and inflammatory index. (3) The levels of IL-1βa?nd IL-18 of NLRP3 inflammasome signalling pathway downstream in plasma of acute gouty arthritis patients and healthy individuals using enzyme linked immunosorbent assay (ELISA). (4) The levels of ASC and caspase-1 of NLRP3 inflammasome proteins were examined by Western Blot. And the differences of proteins levels in two groups were compared.Results: The expression of ASC mRNA in AGA increased significantly compare to healthy individuals (0.0292±0.0214 vs 0.0095±0.0069,P<0.01), the expression of NLRP3 and caspase-1 mRNA were significantly lower in patients with AGA compared with healthy individuals (0.0625±0.0841 vs 0.1330±0.1060, P< 0.05; 0.0247±0.0137 vs 0.1170±0.1560,P<0.01). Moreover, The ASC mRNA in AGA patients was associated significantly with NLRP3 mRNA (r=-0.450, P<0.05) and caspase-1 (r=0.604, P<0.01). Furthermore, the expression of ASC mRNA was found to correlate significantly with globulin (r=-0.547, P<0.05) and very low density lipoprotein cholesterol (r= -0.540, P<0.05) in AGA patients, and caspase-1 correlated significantly to globulin (r=-0.773, P<0.01) and very low density lipoprotein cholesterol (r=-0.465, P<0.05). Expression of IL-1βmRNA in AGA decreased significantly compare to healthy individuals (0.215±0.225 vs 0.761±0.704,P<0.05), but IL-1βl?evels and IL-18 levels in plasma increased significantly compare to healthy individuals (35.37±4.89 vs 31.62±2.19,P<0.05; 2508.14±334.56 vs 1796.93±159.71, P<0.01). The levels of ASC protein in AGA patients were significantly lower compared with healthy individuals (1.229±0.170 vs 1.977±0.163,P<0.01), caspase-1 protein levels decreased significantly compared with healthy individuals (0.786±0.074 vs 1.159±0.196,P<0.05).Conclusion: Dysregulated expression of NLRP3 inflammasome in PBMC of patients with acute gouty arthritis was involved in pathogenesis of gouty inflammation.