阿托伐他汀对脂多糖诱导的THP-1巨噬细胞炎症因子分泌的影响及机制  

The Effect and Mechanism of Atorvastatin on the THP-1 Macrophage Proinflammatory Cytokines Secretion Induced by Lipopolysaccharide

作　　者：喻思扬 曾高峰[1] 刘洋[1] 徐健强[1] 曾梦雅[1] 唐业华 曾志英[3] 石小桥[3] 陈莹[3] 王燕[3] 赵国军[4] 

机构地区：[1]南华大学附属第二医院心血管内科,湖南省衡阳市421001 [2]衡阳市中心医院,湖南省衡阳市421001 [3]南华大学附属第二医院麻醉科,湖南省衡阳市421001 [4]桂林医学院组胚教研室,广西桂林市541004

出　　处：《中国动脉硬化杂志》2016年第7期663-667,共5页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金资助项目(81200218);湖南省自然科学基金课题(14JJ5016)

摘　　要：目的观察阿托伐他汀对脂多糖(LPS)诱导的THP-1巨噬细胞炎症因子分泌的影响,并探讨其机制。方法 100 nmol/L佛波酯孵育THP-1细胞24 h,使其分化为巨噬细胞后,换无血清培养基,加入LPS和(或)阿托伐他汀进行处理。酶联免疫吸附法检测细胞上清液中白细胞介素1β(IL-1β)和白细胞介素18(IL-18)含量,荧光定量PCR检测细胞核苷酸结合寡聚化结构域样受体蛋白1(NLRP1)炎性体的mRNA表达,Western blot检测细胞NLRP1炎性体的蛋白表达。结果阿托伐他汀可呈浓度、时间依赖性抑制LPS诱导的THP-1巨噬细胞IL-1β和IL-18释放;阿托伐他汀可下调THP-1巨噬细胞NLRP1炎性体mRNA和蛋白的表达。结论阿托伐他汀抑制巨噬细胞炎症因子分泌,其作用机制可能与其下调NLRP1炎性体表达有关。Aim To investigate the effect and potential mechanism of atorvastatin on the THP-1 macrophage proinflammatory cytokines release induced by lipopolysaccharide（ LPS）. Methods THP-1 cells were treated with phorbol 12-myristate 13-acetate（ 100 nmol / L） for 24 h to differentiate into macrophages. The medium was then replaced with serum-free medium containing LPS and（ or） atorvastatin. The secretion of interleukin-1β（ IL-1β） and interleukin-18（ IL-18） were quantitated using enzyme-linked immunosorbent assay analysis. The mRNA level of nucleotide-binding oligomerization domain-like receptor protein 1（ NLRP1） inflammasome was measured by real-time PCR. Western blot was employed to analyze the protein expression of NLRP1 inflammasome. Results Atorvastatin inhibited IL-1β and IL-18 secretion induced by LPS in THP-1 macrophages in a dose- and time-dependent manner. Atorvastatin decreased the mRNA and protein expression of NLRP1 inflammasome in THP-1 macrophages. Conclusion Atorvastatin reduces proinflammatory cytokines release from macrophages,and the mechanism might be related to the inhibition of NLRP1 inflammasome expression.

关 键 词：阿托伐他汀 抗炎效应 核苷酸结合寡聚化结构域样受体蛋白1炎性体 动脉粥样硬化 

分 类 号：R5[医药卫生—内科学]