痛风患者血小板来源NLRP3和高迁移率族蛋白1的表达水平及临床意义

Expression levels and clinical significance of NLRP3 and HMGB1 derived from platelets in patients with gout

目的探讨痛风患者血小板来源含pyrin结构域NOD样受体家族3(NLRP3)与高迁移率族蛋白1(HMGB1)的表达水平,以及两者在痛风中的临床意义。方法收集2022年1月至2023年1月青海大学附属医院风湿免疫科痛风性关节炎(GA)男性患者25例,高尿酸血症(HUA)男性患者23例,同时于医院体检中心选取年龄相匹配的男性健康对照(HC)者15例。提取所有研究对象血小板,采用流式细胞术(FCM)检测血小板来源NLRP3、HMGB1的表达水平。同时收集所有研究对象的一般资料及实验室指标,并对NLRP3、HMGB1与其实验室指标进行Pearson线性相关和Spearman秩相关分析。结果GA组NLRP3、HMGB1阳性细胞率高于HUA组、HC组,HUA组高于HC组,差异有统计学意义(P<0.05)。GA组身体质量指数(BMI)、红细胞沉降率(ESR)、C反应蛋白(CRP)、中性粒细胞计数(NEUT)、血小板计数(PLT)、血尿酸(UA)、纤维蛋白原(FIB)、D-二聚体(DD)水平高于HUA组、HC组,HUA组BMI、PLT、UA水平高于HC组(P<0.05);GA组饮酒比例、三酰甘油(TG)水平高于HC组,HUA组饮酒比例、TG水平高于HC组(P<0.05);GA组血小板平均体积(MPV)水平低于HC组(P<0.05)。GA组NLRP3阳性细胞率分别与ESR、CRP、NEUT、PLT、TG、UA、FIB、DD呈正相关,与MPV呈负相关(P<0.05);GA组HMGB1阳性细胞率分别与CRP、NEUT、PLT、TG、FIB、DD呈正相关(P<0.05);HUA组NLRP3阳性细胞率分别与PLT、TG、UA呈正相关(P<0.05);HUA组HMGB1阳性细胞率分别与PLT、TG呈正相关(P<0.05)。结论血小板来源的NLRP3、HMGB1可间接反映痛风患者体内炎症及疾病的活动程度,可能参与了痛风的发生及发展,或有望成为评估痛风的生物学指标。

Objective To investigate the expression levels of NOD-like receptor family pyrin domain-containing 3(NLRP3)and high mobility group box-1 proten(HMGB1)in platelets derived from patients with gout,as well as their clinical significance in gout.Methods A total of 25 male patients with gout arthritis(GA),23 male patients with hyperuricemia(HUA),and 15 age-matched male healthy controls(HC)were recruited from the Department of Rheumatology and Immunology,Affiliated Hospital of Qinghai University from January 2022 to January 2023.Platelet samples were obtained from all subjects and the expression levels of platelet-derived NLRP3 and HMGB1 were detected using flow cytometry(FCM).General information and laboratory indicators of all subjects were collected,and Pearson linear correlation and Spearman rank correlation analysis were performed between NLRP3,HMGB1 and their laboratory indicators.Results The positive cell rates of NLRP3 and HMGB1 in GA group were higher than those in HUA group and HC group,while those in HUA group were higher than those in HC group,with statistically significant differences(P<0.05).In GA group,body mass index(BMI),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),neutrophil count(NEUT),platelet count(PLT),blood uric acid(UA),fibrinogen(FIB),D-dimer(DD)levels were higher than those in HUA group and HC group,while BMI,PLT,and UA levels in HUA group were higher than those in HC group(P<0.05);the proportion of alcohol drinkers,and level of triacylglycerol(TG)in GA group were higher than those in HC group,while those level in HUA group were higher than those in HC group(P<0.05);mean platelet volume(MPV)level in GA group was lower than that in HC group(P<0.05).In GA group,the positive cell rate of NLRP3 was positively correlated with ESR,CRP,NEUT,PLT,TG,UA,FIB,and DD(P<0.05),and negatively correlated with MPV(P<0.05);the positive cell rate of HMGB1 was positively correlated with CRP,NEUT,PLT,TG,FIB,and DD(P<0.05);in HUA group,the positive cell rate of NLRP3 was positively correlated with PLT,TG,and UA(P<0.05);the positive cell rate of HMGB1 was positively correlated with PLT and TG(P<0.05).Conclusion Platelet-derived NLRP3 and HMGB1 may indirectly reflect the degree of inflammation and disease activity in gout patients,be involved in the development and progression of gout.They are expected to become biological indicators for assessing gout in the future.