CAJ | 학술논문

目的：探讨辛伐他汀对氧化低密度脂蛋白( oxidized low density lipoprotein, oxLDL )诱导的巨噬细胞内活性氧( ROS)的水平及IL-1β分泌的影响。方法将oxLDL 0、50、100、200 mg·L-1作用于巨噬细胞J774A.1后,采用油红O染色观察脂滴在巨噬细胞内的聚集情况；用辛伐他汀0．5、1．0μmol·L-1作用于oxLDL处理的巨噬细胞,流式细胞仪检测辛伐他汀作用前后细胞内ROS的水平；Western blot检测pro-caspase-1、cleaved caspase-1和成熟 IL-1β的表达情况。结果油红O染色结果表明,oxLDL可导致巨噬细胞内明显的脂质聚集,并于100 mg·L-1作用剂量达到摄取脂质的饱和状态；流式细胞仪结果表明,oxLDL可以诱导脂质聚集巨噬细胞内ROS的水平增加,辛伐他汀作用后,ROS水平由(167±0．47)%下降到(139±0．97)%,并呈明显的剂量依赖；Western blot结果表明,辛伐他汀可抑制oxLDL诱导的caspase-1活化及IL-1β的分泌,辛伐他汀处理组与oxLDL实验组相比,cleaved caspase-1及成熟 IL-1β的表达呈下降趋势,灰度值差异有统计学意义( P<0．05)。结论在oxLDL诱导的巨噬细胞脂质聚集模型中,辛伐他汀可以抑制巨噬细胞内ROS的产生及caspase-1的活化,并减少IL-1β的分泌。
목적：탐토신벌타정대양화저밀도지단백( oxidized low density lipoprotein, oxLDL )유도적거서세포내활성양( ROS)적수평급IL-1β분비적영향。방법장oxLDL 0、50、100、200 mg·L-1작용우거서세포J774A.1후,채용유홍O염색관찰지적재거서세포내적취집정황；용신벌타정0．5、1．0μmol·L-1작용우oxLDL처리적거서세포,류식세포의검측신벌타정작용전후세포내ROS적수평；Western blot검측pro-caspase-1、cleaved caspase-1화성숙 IL-1β적표체정황。결과유홍O염색결과표명,oxLDL가도치거서세포내명현적지질취집,병우100 mg·L-1작용제량체도섭취지질적포화상태；류식세포의결과표명,oxLDL가이유도지질취집거서세포내ROS적수평증가,신벌타정작용후,ROS수평유(167±0．47)%하강도(139±0．97)%,병정명현적제량의뢰；Western blot결과표명,신벌타정가억제oxLDL유도적caspase-1활화급IL-1β적분비,신벌타정처리조여oxLDL실험조상비,cleaved caspase-1급성숙 IL-1β적표체정하강추세,회도치차이유통계학의의( P<0．05)。결론재oxLDL유도적거서세포지질취집모형중,신벌타정가이억제거서세포내ROS적산생급caspase-1적활화,병감소IL-1β적분비。
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.