NLRP3炎性小体对冠心病患者血浆IL-1β、IL-18、TGF-β水平的影响

Effect of NLRP3 inflammasome on plasma interleukin-1β,interleukin-18 and transforming growth factor-βlevels in patients with coronary heart disease

目的探讨核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎性小体对冠心病患者血浆白细胞介素(IL)-1β、IL-18、转化生长因子-β(TGF-β)水平的影响。方法入选健康对照组30例及冠心病组60例,采用RT-qPCR、Western blot法分别检测外周血单个核细胞(PBMCs)中NLRP3、凋亡相关微粒蛋白(ASC)、半胱氨酸蛋白酶-1(caspase-1)mRNA及蛋白表达水平,ELISA法检测血浆中IL-1β、IL-18、TGF-β水平。结果 ASC mRNA、NLRP3、ASC、caspase-1表达水平及血浆IL-1β、IL-18、TGF-β水平在两组之间差异有统计学意义(P<0.05)。冠心病组患者NLRP3mRNA和caspase-1mRNA均与IL-18呈正相关(r=0.327、0.274,P=0.011、0.031),ASC与年龄、IL-1β、IL-18呈正相关(r=0.370、0.467、0.403,P=0.024、0.009、0.027);caspase-1与吸烟、IL-18呈正相关(r=0.613、0.414,P<0.01,P=0.023),IL-1β与TGF-β呈负相关(r=-0.287,P=0.026)。结论以NLRP3炎性小体为中心的NLRP3-ASC-caspase-1-IL-1β/IL-18信号通路可能在冠心病的发生发展过程中发挥重要作用,但该通路并未促进冠心病患者抗炎因子TGF-β的表达。

Objective To investigate the effect of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome on plasma interleukin-1β(IL-1β),interleukin-18(IL-18)and transforming growth factor-β(TGF-β)levels in the patients with coronary heart disease(CHD).Methods Thirty healthy controls and 60 patients with CHD were recruited.The expression levels of NLRP3,apoptosis-associated speck-like protein containing CARD(ASC)and caspase-1 mRNA as well as protein in peripheral blood mononuclear cells(PBMCs)were detected by adopting RT-qPCR and Western blot respectively,and the levels of plasma IL-1β,IL-18 and TGF-βwere detected by the ELISA method.Results The expression levels of NLRP3,ASC and caspase-1 in PBMCs,and plasma IL-1β,IL-18,TGF-βhad statistical difference between the CHD group and control group(P<0.05).Both NLRP3 mRNA and caspase-1 mRNA were positively correlated with IL-18 in the CHD group(r=0.327,0.274,P=0.011、0.031);ASC was positively correlated with age,IL-18 and IL-1βin the CHD group(r=0.370,0.467,0.403,P=0.024、0.009、0.027);caspase-1 was positively correlated with smoking and IL-18 in the CHD group(r=0.613,0.414,P<0.01,P=0.023);IL-1βwas negatively correlated with TGF-βin the CHD group(r=-0.287,P=0.026).Conclusion NLRP3-ASC-caspase-1-IL-1β/IL-18 signal pathway with the NLRP3 inflammasome as the center may play an important role in the occurrence and development of CHD,but this signal pathway does not promote the expression of anti-inflammatory cytokine TGF-βin the patients with CHD.