Nod样受体蛋白3与非瓣膜性心房颤动患者左心房血栓形成的相关性

Relationship between NLRP3 and left atrial thrombosis in non-valvular AF patients

目的探讨Nod样受体蛋白3(NLRP3)炎性小体与非瓣膜性心房颤动(NVAF)患者左心房血栓形成的相关性及预测价值。方法选取我院收治的怀疑存在左心房血栓的NVAF患者260例,根据食管心脏超声检查结果分为血栓组55例和非血栓组205例。检测外周血单核细胞(PBMC)中NLRP3、半胱氨酸天冬氨酸蛋白酶1(caspase-1)mRNA和蛋白表达及相关细胞因子白细胞介素(IL)1β、IL-18水平,分析NVAF患者左心房血栓形成的独立危险因素,绘制ROC曲线分析NLRP3炎性小体对NVAF患者左心房血栓形成的预测价值。结果与非血栓组比较,血栓组短暂性脑缺血发作/脑卒中、持续性心房颤动、CHADS2评分、CHA2DS2-VASc评分、IL-1β及IL-18水平明显升高,心房颤动病程更长,PBMC中NLRP3、caspase-1mRNA及蛋白表达水平明显升高(P<0.05,P<0.01)。持续性心房颤动、心房颤动病程、CHA2DS2-VASc评分、CHADS2评分、NLRP3mRNA及caspase-1mRNA是血栓形成的独立危险因素(P<0.05,P<0.01)。相关性分析显示,血栓组NLRP3 mRNA水平与NLRP3蛋白表达、caspase-1mRNA和蛋白表达、IL-1β、IL-18、持续性心房颤动、心房颤动病程、CHADS2评分及CHA2DS2-VASc评分呈正相关(r=0.890,r=0.905,r=0.904,r=0.862,r=0.827,r=0.706,r=0.742,r=0.762,r=0.690,P<0.01)。ROC曲线显示,NLRP3炎性小体曲线下面积为0.891(95%CI:0.837~0.944),阈值点为1.90,敏感性和特异性分别为79.03%和84.51%。结论 PBMC中NLRP3炎性小体在NVAF并发左心房血栓形成患者中表达明显升高,可作为左心房血栓形成的独立危险因素,对评估NVAF并发左心房血栓形成有一定价值。

Objective To study the relationship between NLRP3 inflammatory corpuscles and left atrial thrombosis in non-valvular AF patients.Methods Two hundred and sixty non-valvular AF patients with suspected left atrial thrombosis admitted to our hospital were divided into thrombosis group(n=55)and thrombosis-free group(n=205)according to their transesophageal echocardiography.The expressions of NLRP3 and caspase-1 mRNA and protein were detected and the serum levels of IL-1βand IL-18 were measured.The independent risk factors for left atrial thrombosis were analyzed by logistic regression analysis.The value of NLRP3 inflammatory corpuscles for predicting left atrial thrombosis in non-valvular AF patients was analyzed according to their ROC curve.Results The incidence of TIA,cerebral stroke and persistent AF,CHADS2 and CHA2 DS2-VASc scores,and serum IL-1βand IL-18 levels were significantly higher,the duration of AF was significantly longer,the number of PBMC was significantly greater,the expression levels of NLRP3 and caspase-1 mRNA and protein were significantly higher in thrombosis group than in thrombosis-free group(P<0.05,P<0.01).Persistent AF,duration of AF,CHA2 DS2-VASc,CHADS2 score,NLRP3 and caspase-1 expression levels were the independent risk factor for thrombosis in non-valvular AF patients(P<0.05,P<0.01).Spearman correlation analsis showed that the serum NLRP3 mRNA level was positively related with the expressions of NLRP3 protein and caspases-1 mRNA and protein,serum IL-1βand IL-18 levels,persistent AF,duration of AF,CHADS2 and CHA2 DS2-VASc score(r=0.890,r=0.905,r=0.904,r=0.862,r=0.827,r=0.706,r=0.742,r=0.762,r=0.690,P<0.01).ROC curve analysis showed that the area under ROC curve for NLRP3 inflammatory corpucles was 0.891(95%CI:0.837-0.944)with a threshold point of 1.90,a sensiticity of 79.03%and a specificity of 84.51%.Conclusion Elevated expression level of NLRP3 inflammatory corpuscles is the risk factor for left atrial thrombosis and plays a certain role in assessing left atrial thrombosis in non-valvular AF patients.