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目的:探讨核苷酸结合寡聚化结构域样受体蛋白1(NLRP1)炎性体在阿托伐他汀抑制THP-1巨噬细胞白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)分泌中的作用。方法:用10μg/L脂多糖诱导THP-1巨噬细胞分泌IL-1β和IL-18,以不同浓度阿托伐他汀(1、10和20μmol/L)孵育细胞24 h,或以10μmol/L阿托伐他汀处理细胞不同时间(12、24和48 h),或转染NLRP1 siRNA以沉默细胞内NLRP1的表达。采用RT-PCR检测细胞内NLRP1炎性体mRNA的表达,Western blot检测细胞内NLRP1炎性体蛋白的表达,ELISA检测细胞上清液中IL-1β和IL-18的含量。结果:阿托伐他汀可抑制THP-1巨噬细胞NLRP1炎性体mRNA和蛋白的表达,且这种效应呈浓度和时间依赖性。转染NLRP1 siRNA后,THP-1巨噬细胞NLRP1的蛋白表达明显下降,且阿托伐他汀对IL-1β和IL-18分泌的抑制作用明显增强。结论:阿托伐他汀通过抑制NLRP1炎性体表达减少巨噬细胞IL-1β和IL-18的释放,发挥抗炎作用,进而延缓动脉粥样硬化进展。
OBJECTIVE: To investigate the effect of atorvastatin on IL-1β (IL-1β) and interleukin-1β (IL-1β) in THP-1 macrophages induced by NLRP1 inflammasome. 18 (IL-18) secretion. Methods: IL-1β and IL-18 secreted by THP-1 macrophages were induced by lipopolysaccharide (LPS) (10μg / L), and the cells were incubated with atorvastatin (1,10 and 20μmol / Atorvastatin treated cells at different times (12, 24 and 48 h), or transfected NLRP1 siRNA to silence the expression of intracellular NLRP1. The expression of NLRP1 inflammasome mRNA was detected by RT-PCR. The expression of NLRP1 inflammasome protein was detected by Western blot. The levels of IL-1β and IL-18 in the supernatant of the cells were detected by ELISA. Results: Atorvastatin inhibited the mRNA and protein expression of NLRP1 inflammasome in THP-1 macrophages, and the effect was concentration-dependent and time-dependent. After transfected with NLRP1 siRNA, the protein expression of NLRP1 in THP-1 macrophages was significantly decreased, and atorvastatin significantly inhibited the secretion of IL-1β and IL-18. Conclusion: Atorvastatin can reduce the release of IL-1β and IL-18 in macrophages by inhibiting the expression of NLRP1 inflammasome and exert anti-inflammatory effects, which in turn delay the progression of atherosclerosis.