摘要
目的 探讨黑素瘤缺乏因子2(AIM2)、胱天蛋白酶-1(Caspase-1)和焦孔素D(GSDMD)在急性痛风性关节炎(AGA)中的表达及意义.方法 选取30例AGA患者(AGA组)和30例男性健康体检者(HC组),血细胞分析仪检测血清白细胞计数(WBC)、血红蛋白(Hb)、血小板计数(PLT),自动生化分析仪检测空腹血糖(FBG)、血尿酸(UA)、三酰甘油(TG)、总胆固醇(TC)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、血清肌酐(Scr)、尿素氮(BUN)、肌酐清除率(Ccr)、红细胞沉降率(ESR)和C-反应蛋白(CRP)水平.荧光定量法检测2组样本血清双链DNA(dsDNA)水平;Western blot法检测2组外周血单个核细胞(PBMCs)中AIM2、Caspase-1、GSDMD、白细胞介素(IL)-1β和IL-18蛋白表达水平;酶联免疫吸附试验检测血清IL-1β和IL-18表达水平.结果 与HC组比较,AGA组WBC、PLT、ESR、CRP、UA、TC、TG、Scr、Ccr水平增加,血清中dsDNA、IL-1β、IL-18相对表达水平增加,PBMCs中AIM2、Caspase-1、GSDMD、IL-1β、IL-18蛋白相对表达水平均增加(P＜0.05).PBMCs中,AIM2蛋白的表达水平与Caspase-1、GSDMD、IL-1β和IL-18蛋白表达水平均呈正相关(r或rs分别为0.965、0.986、0.928及0.737,均P＜0.01).结论 AIM2炎症小体介导的细胞焦亡通路相关分子(AIM2/Caspase-1/GSDMD)在AGA中表达增高,其可能参与AGA的免疫炎症反应.
Abstract
Objective To investigate the expression and role of melanoma 2(AIM2),Caspase-1 and gasdermin D(GSDMD)in the pathogenesis of acute gouty arthritis(AGA).Methods Clinical data,biochemical indices and blood samples were collected from 30 patients with AGA(the AGA group)and 30 healthy volunteers(the HC group).Blood cell analyzer was used to detect serum white blood cell count(WBC),hemoglobin(Hb)and platelet count(PLT).Automatic biochemical analyzer was used to detect fasting blood glucose(FBG),blood uric acid(UA),triacylglycerol(TG),total cholesterol(TC),alaine transaminase(ALT),aspartate transaminase(AST),serum creatinine(Scr),blood urea nitrogen(BUN),creatinine clearance rate(Ccr),erythrocyte sedimentation rate(ESR)and C-reactive protein(CRP)levels.Fluorescence quantitative assay was used to measure serum level of double-stranded DNA(dsDNA).Western blot was performed to detect the relative protein expression levels of AIM2,Caspase-1,GSDMD,interleukin-1β(IL-1β)and IL-18 in peripheral blood mononuclear cells(PBMCs).Enzyme-linked immunosorbent assay(ELISA)was used to measure serum levels of IL-1β and IL-18.Results Compared with the HC group,the AGA group showed increased levels of blood biochemical indicators,including WBC,PLT,ESR,CRP,UA,TC,TG,Scr and Ccr(P＜0.05).The serum levels of dsDNA,IL-1β and IL-18 were also increased in the AGA group.Furthermore,the relative protein expression levels of AIM2,Caspase-1,GSDMD,IL-1β and IL-18 in PBMCs were all increased(P＜0.05).In PBMCs,the protein expression level of AIM2 was positively correlated with that of Caspase-1,GSDMD,IL-1β and IL-18(r or rs values were 0.965,0.986,0.928 and 0.737,respectively,all P＜0.01).Conclusion The expression of AIM2 inflammasome-mediated pyroptosis pathway related molecules(AIM2/Caspase-1/GSDMD)is increased in AGA,which may be involved in the immune inflammatory response of AGA.
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