Effect of simvastatin on production of reactive oxygen species and secretion of IL-1βin macrophages induced by oxLDL / 中国药理学通报

ABSTRACT

Aim To study the effect of simvastatin on the production of reactive oxygen species ( ROS ) and the secretion of interleukin-1 beta ( IL-1β) in oxidized low density lipoprotein ( oxLDL )-induced macropha-ges. Methods After the murine macrophage J774A. 1 was treated with 0,50,100,200 mg·L-1 oxLDL, the contents of aggregated lipid in macrophages were ob-served and determined by oil red O staining. Then, the oxLDL-primed macrophages were treated with 0 . 5 ,1 . 0μmol·L-1 simvastatin, the production of ROS was de-termined by flow cytometry and the expressions of pro-caspase-1 , cleaved caspase-1 and mature IL-1βon pro-tein level were determined by Western blot. Results The oil red O staining results showed that oxLDL could induce obvious lipid aggregation in macrophages, and reached the saturation point with 100 mg·L-1 concen-tration. Flow cytometry results indicated that oxLDL could induce the production of ROS in macrophages, up to 167% ± 0. 47%, and ROS level decreased to 139% ± 0. 97% in a dose-dependent manner after treatment with simvastatin. Western blot indicated that simvastatin could inhibit the expression of cleaved caspase-1 and mature IL-1β in macrophages triggered by oxLDL;compared with oxLDL group, the expression of cleaved caspase-1 and mature IL-1β decreased in simvastatin treated group, and all results had statistical significance ( P<0. 05 ) . Conclusion In the lipid ag-gregation model of macrophages induced by oxLDL, simvastatin can inhibit the production of ROS, caspase-1 activation, and secretion of IL-1β in macrophages.