SREBP1在阿托伐他汀抑制NLRP1炎性体表达中的作用  

Role of SREBP1 in atorvastatin-induced reduction of NLRP1 inflammasome expression

作　　者：王波[1] 喻思扬 刘洋[1] 王燕[2] 徐健强[1] 曾高峰[1] 赵国军[3] WANG Bo YU Si-Yang LIU Yang WANG Yah XU Jian-Qiang ZENG Gao-Feng ZHAO Guo-Jun(Department of Cardiovascular Medicine, the Second Affiliated Hospital, University of South China, Hengyang 421000, China)

机构地区：[1]南华大学附属第二医院心血管内科,衡阳421000 [2]南华大学附属第二医院麻醉科,衡阳421000 [3]桂林医学院组胚教研室,桂林541004

出　　处：《中国免疫学杂志》2016年第12期1805-1808,1814,共5页Chinese Journal of Immunology

基　　金：湖南省自然科学基金(No.14JJ5016)

摘　　要：目的:探讨固醇调节元件结合蛋白1(SREBP1)在阿托伐他汀抑制核苷酸结合寡聚化结构域样受体蛋白1(NLRP1)炎性体表达中的作用。方法:160 nmol/L佛波酯孵育THP-1细胞12 h,使其分化为巨噬细胞,更换无血清培养基,加入脂多糖和(或)阿托伐他汀进行处理。Real-time PCR检测细胞中NLRP1、SREBP1 mRNA的表达;Western blot检测细胞中NLRP1、SREBP1蛋白的表达;检测SREBP1 siRNA预处理细胞后对阿托伐他汀抑制NLRP1表达的影响。结果:阿托伐他汀能抑制THP-1巨噬细胞NLRP1和SREBP1的mRNA和蛋白的表达;单独使用SREBP1 siRNA处理细胞可有效抑制NLRP1的表达,且与单独使用阿托伐他汀无明显差异;同时使用SREBP1 siRNA和阿托伐他汀处理细胞比单独使用一种对NLRP1的抑制作用更为显著。结论:阿托伐他汀可能通过SREBP1途径抑制NLRP1的表达,进而发挥抗炎效应。Objective： To investigate the role of sterol regulatory element binding protein-1（ SREBP1） in atorvastatin-induced reduction of nucleotide-binding oligomerization domain-like receptor protein 1（ NLRP1） inflammasome expression. Methods： THP-1cells were treated with phorbol 12-myristate 13-acetate（ 160 nmol / L） for 12 h to be differentiated into macrophages. The medium was then replaced with serum-free medium containing lipopolysaccharide and（ or） atorvastatin. The mRNA expression of NLRP1 and SREBP1 were detected by Real-time PCR. The protein expression of NLRP1 and SREBP1 were determined by Western blot. Furthermore,we observed the effect of SREBP1 siRNA on atorvastatin-induced reduction of NLRP1 expression. Results： Atorvastatin inhibited the mRNA and protein expression of NLRP1 and SREBP1 in the THP-1 macrophages. SREBP1 siRNA showed no significant difference on lowering NLRP1 expression when compared with atorvastatin. Treating cells with SREBP1 siRNA and atorvastatin at the same time resulted in more obvious reduction of NLRP1 expression than single use of SREBP1 siRNA or atorvastatin. Conclusion：Atorvastatin might exert anti-inflammatory effect by repressing NLRP1 expression through the SREBP1 pathway.

关 键 词：阿托伐他汀 抗炎作用 SREBP1 NLRP1炎性体 动脉粥样硬化 

分 类 号：R392.5[医药卫生—免疫学]