NLRP3-ASC-Caspase-1信号通路在慢性心力衰竭患者外周血单核细胞中的表达

Changes of NLRP1⁃ASC⁃Caspase⁃1 signaling pathways in peripheral blood monocytes from patients with atrial fibrillation

目的:通过检测慢性心力衰竭患者外周血单核细胞(peripheral blood mononuclear cells,PBMCs)NLRP3信号通路的表达水平,探讨NLRP3信号通路和其诱导的炎症反应在不同类型慢性心力衰竭患者的PBMCs中的表达。方法:选择本院2018年10月~2019年12月收治的Ⅱ、Ⅲ、Ⅳ级慢性心衰患者(NYHAⅡ~Ⅳ级)各20例为Ⅱ、Ⅲ、Ⅳ组,选择20名健康人为对照组。采集所有受试者外周静脉血,分别提取血浆和单核细胞,磁珠分选法鉴定单核细胞,运用实时荧光定量聚合酶链反应(qRT-PCR)和蛋白质免疫印迹(Western blot)法检测PBMCs中NLRP3、ASC、Caspase-1的mRNA和蛋白的表达水平,酶联免疫吸附(ELISA)法检测血浆中白细胞介素-1β(IL-1β)的水平。结果:与对照组比较,Ⅱ、Ⅲ、Ⅳ组PBMCs中NLRP3、ASC、Caspase-1蛋白表达与mRNA水平增高(P<0.05),与Ⅱ组比较,Ⅲ、Ⅳ组这些指标的表达增加(P<0.05),与Ⅲ组比较,Ⅳ组这些指标的表达增加(P<0.05)。与对照组比较,Ⅱ、Ⅲ、Ⅳ组血浆中的IL-1β水平增高(P<0.05),与Ⅱ组比较,Ⅲ、Ⅳ组IL-1β表达增加(P<0.05),与Ⅲ组比较,Ⅳ组IL-1β表达增加(P<0.05)。结论:NLRP3-ASC-Caspase-1信号通路可能引起心力衰竭患者体内的慢性炎症并在慢性心力衰竭病情进展中发挥作用。

Objective:To detect the expression of NLRP3 signal pathway in peripheral blood mononuclear cells(PBMCs)of patients with chronic heart failure,and to explore the expression of NLRP3 signal pathway and its induced inflammatory response in PBMCs of patients with different types of chronic heart failure.Methods:Patients with chronic heart failure(NYHAⅡ~Ⅳ),admitted to our hospital from 2019 to 2020 were included.The paatients mere divided into groups,including theⅡgroup,theⅡgroup and theⅣgroup according to NYHA classification,and 20 normal subjects were selected as the control group.The peripheral venous blood of all subjects was collected,and the plasma and monocytes were extracted,respectively.The monocytes were identified by magnetic beads sorting.The mRNA and protein expression levels of NLRP3,ASC and Caspase⁃1 in PBMCs were detected by real⁃time fluorescence quantitative polymerase chain reaction(qRT⁃PCR)and Western blot,and the level of in⁃terleukin⁃1β(IL⁃1β)in plasma was detected by enzyme⁃linked immunosorbent assay(ELISA).Results:Compared with the con⁃trol group,the expression of NLRP3,ASC,Caspase⁃1 protein and mRNA in PBMCs of patients with gradeⅡ,ⅢandⅣin⁃creased.Compared with patients with gradeⅡ,the expression of these indexes increased in patients with gradeⅢandⅣ.Com⁃pared with patients with gradeⅢ,the expression of these indexes increased in patients with gradeⅣ.Compared with the control group,the plasma levels of IL⁃1βin patients with gradeⅡ,ⅢandⅣwere higher than those in patients with gradeⅡ,ⅢandⅣ(P<0.05).The expression of these indexes in patients with gradeⅢandⅣwas higher than that in patients with gradeⅢ(P<0.05).Conclusion:The results suggest that NLRP3⁃ASC⁃Caspase⁃1 signal pathway may cause chronic inflammation in patients with heart failure and play a role in the progression of chronic heart failure.