AIM2 Inflammasomes Mediated Pyroptosis Expression In Peripheral Blood Mononuclear Cells Of Patients With Gouty Arthritis

Objective: To compare the expression of the absent in melanoma 2(AIM2)inflammasome in the peripheral blood mononuclear cells(PBMCs)of patients with acute gouty arthritis,hyperuricemia and healthy controls,and to analyze its correlation with laboratory indicators,so as to explore its role in the pathogenesis of gouty arthritis.Methods: 30 patients with acute gouty arthritis and 30 patients with hyperuricemia were recruited and divided into acute gouty arthritis group(AGA group)and hyperuricemia group(HU group),and 30 healthy subjects matched for age and gender were selected as healthy control group(HC group).Clinical data such as age,gender,height and weight were collected.Routine blood test,erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),uric acid(UA),blood glucose(BG),blood lipid,liver function,kidney function and other laboratory indicators were collected.The levels of serum ds DNA were detected by fluorescence quantitative method.The m RNA expression levels of AIM2,Caspase-1 and Gasdermin D(GSDMD)in PBMCs were detected by real-time PCR.ELISA was used to detect the levels of IL-1β and IL-18 in serum.The correlation of AIM2 inflammasome components and the correlation between laboratory indicators were analyzed.Results:(1)There was no significant difference in age among the three groups(P >0.05).There were no significant differences in BG,alanine aminotransferase(ALT),aspartate aminotransferase(AST),and blood urea nitrogen(BUN)among the three groups(P > 0.05).Body mass index(BMI),UA,total cholesterol(TC)and triglyceride(TG)were significantly higher in AGA group and HU group than in HC group(P < 0.01),but there was no significant difference between AGA group and HU group(P > 0.05).The white blood cell count(WBC),platelet count(PLT),ESR and CRP level in AGA group were significantly higher than those in HU group and HC group(P < 0.05),and there was no significant difference between HU group and HC group(P > 0.05).The serum creatinine(Scr)level in AGA group was significantly higher than that in HU group and HC group(P < 0.05).The level of creatinine clearance(Ccr)in AGA group and HU group was significantly higher than that in HC group(P < 0.05).(2)The serum level of ds DNA in AGA group was significantly higher than that in HU group and HC group(P < 0.05),but there was no significant difference between HU group and HC group(P > 0.05).(3)The expression of AIM2 m RNA in PBMCs of AGA group was significantly higher than that of HU group and HC group(P < 0.05),and HU group was significantly higher than that of HC group(P < 0.05).The expression of Caspase-1 m RNA in PBMCs of AGA group was significantly higher than that of HC group(P < 0.05),and there was no significant difference between HU group and AGA group(P > 0.05).The expression of Caspase-1 m RNA in HU group was significantly higher than that of HC group(P < 0.05).The expression level of GSDMD m RNA in PBMCs in AGA group was significantly higher than that in HU group and HC group(P < 0.05),and HU group was significantly higher than that in HC group(P < 0.05).(4)The serum level of IL-1β in AGA group was significantly higher than that in HC group(P < 0.01),but there was no significant difference between AGA group and HU group(P >0.05),and there was no significant difference between HU group and HC group(P > 0.05).The serum levle of IL-18 in AGA group was significantly higher than that in HC group(P < 0.01),but there was no significant difference between HU group and AGA group(P >0.05).The serum IL-18 level in HU group was significantly higher than that in HC group(P < 0.01).(5)The m RNA expression level of AIM2 in patients with acute gouty arthritis was positively correlated with the m RNA expression level of Caspase-1 and GSDMD(P <0.05).There was no correlation between AIM2 m RNA expression level and serum IL-1β level(P > 0.05),but it was positively correlated with serum IL-18 level(P < 0.05).The m RNA expression level of Caspase-1 was positively correlated with the m RNA expression level of GSDMD(P < 0.05),but was not correlated with the serum level of IL-1βand IL-18(P > 0.05).The m RNA expression level of GSDMD was not correlated with the serum level of IL-1β(P > 0.05),but was positively correlated with the serum level of IL-18(P < 0.05).(6)AIM2 m RNA expression was positively correlated with ESR,TC and Scr in patients with acute gouty arthritis(P < 0.05).The expression level of Caspase-1 m RNA was positively correlated with Scr level(P < 0.05).The expression level of GSDMD m RNA was positively correlated with ESR,TC and Scr levels(P < 0.05).Serum IL-1β level was positively correlated with PLT,ESR,CRP and UA(P < 0.05).Serum IL-18 level was positively correlated with BMI,WBC,PLT,ESR,CRP,UA,TC and Ccr(P < 0.05).Conclusions: Our study suggests that AIM2 inflammasome mediated pyroptosis,AIM2/Caspase-1/GSDMD pathway,may be involved in the pathogenesis of acute gouty arthritis,which provides a potential target for the treatment of acute gouty arthritis.