NLRP1信号通路在心房颤动发病机制中的作用

Role of NLRP1 inflammasome signaling pathways in development of atrial fibrillation

目的:探索核苷酸结合寡聚化结构域样受体蛋白1(NLRP1)炎症小体信号通路相关蛋白表达与心房颤动(AF)发病的关联性。方法:选取某院收治的房颤患者(AF)40例,其中阵发性房颤(PAF)和非阵发性房颤(nPAF)各20例,另选20例病史和体检均无AF证据的体检者作为对照组(CON组)。通过磁珠分选、实时定量PCR、Western blotting和酶联免疫吸附试验检测受试者NLRP1通路中NLRP1、凋亡相关斑点样蛋白(ASC)及半胱氨酸天冬氨酸蛋白水解酶-1(Caspase-1)的mRNA和蛋白表达水平。结果:3组受试者临床资料比较,差异无统计学意义(P>0.05)。采用CD14^(+)抗体磁珠纯化3组受试者PBMC后,PBMC纯度达90%以上,PAF组NLRP1,ASC,Caspase-1 PBMC mRNA和蛋白表达水平高于CON组,低于nPAF组(P<0.01)。PAF组PBMC中IL-1β表达水平高于CON组,低于nPAF组,差异有统计学意义(P<0.01)。结论:NLRP1信号通路可能引起房颤患者体内慢性炎症,并在房颤病情进展中发挥重要作用。

Objective:As one of the inflammasome components,NLRP1 is involved in a series of physiological and pathological processes.However,its relevance in atrial fibrillation(AF)remains to be elucidated.The aim of this study was to detect NLRP1 inflammasome expression in peripheral blood mononuclear cells(PBMCs)of patients with paroxysmal atrial fibrillation(PAF)and non-paroxysmal atrial fibrillation(nPAF)and its correlation with AF.Methods:A total of 40 patients with PAF(n=20)and nPAF(n=20)were selected,and 20 subjects with no evidence of AF in their medical history and physical examination were used as the normal control group(CON group).Expression of the NLRP1 inflammasome pathway was examined by magnetic bead sorting,real-time quantitative PCR,Western-blotting and enzyme-linked immunosorbent assay(Elisa).Results:The expression of NLRP1 pathway protein and the level of mRNA in PBMC of PAF and nPAF groups were higher than those of the normal control group(P<0.01),and the expression of these indicators in patients in the nPAF group was significantly increased compared with the PAF group(P<0.01).However,the results of serum inflammatory product IL-1βin AF patients were consistent with NLRP1 signaling pathway expression levels.Conclusion:The results suggest that NLRP1 signaling pathway may cause chronic inflammatory response in patients with atrial fibrillation,and play a role in the development of atrial fibrillation.