白细胞介素1β影响人血管平滑肌细胞对美伐他汀的敏感性

Effects of interleukin-1β on the sensitivity of vascular smooth muscle cells to compactin treatments

目的探讨白细胞介素1β(IL-1β)能否干扰人血管平滑肌细胞对美伐他汀的敏感性。方法给予不同浓度美伐他汀(0,1,10,20,50μmol·L-1)单独或联合20μg·L-1IL-1β处理人血管平滑肌细胞24 h,酶法测定细胞内羟甲基戊二酸单酰辅酶A还原酶(HMGCoA-R)的酶活性,并用荧光定量聚合酶链反应(real-time PCR)检测HMGCoA-R的mRNA表达水平。然后选取50μmol·L-1美伐他汀单独或联合20μg·L-1IL-1β处理人血管平滑肌细胞24 h,western blot检测相关基因的蛋白表达。结果美伐他汀呈剂量依赖性抑制人血管平滑肌细胞HMGCoA-R的活性。IL-1β能上调细胞内HMGCoA-R的活性,使同样剂量的美伐他汀在IL-1β存在的条件下,对HMGCoA-R活性的抑制作用显著降低。IL-1β还能促进美伐他汀处理的人血管平滑肌细胞的固醇调节原件结合蛋白2(SREBP2)和SREBPs裂解清除活化蛋白(SCAP)的表达增加,上调细胞的HMGCoA-R的mRNA和蛋白表达。结论 IL-1β能降低人血管平滑肌细胞对美伐他汀的敏感性。

Objective To investigate the effects of interleukin -1β（ IL-1β） on the sensitivity of human vascular smooth muscle cells （ VSMC ） to compactin treatments.Methods VSMC were treated with different concentrations of compactin （0,1,10,20,50 μmol· L-1 ） in the absence or presence of IL -1β（20μg· L-1 ） for 24 h.Commercial kits was used to evaluated the enzymatic activity of HMGCoA reductase.Real-time PCR was used to determine the mRNA.50 μmol· L-1 com-pactin in the presence of IL -1β（20 μg· L-1 ） for 24 h was extracted, and western-blot was adopted to determine protein expression of target genes.Results Compactin inhibited enzymatic activity of HMGCoA in a dose -dependent manner and IL -1βweakened these suppressive effects.IL-1βupregulated enzymatic activity of HMGCoA reductase and was accompanied by increased HMGCoA reductase mRNA.Protein ex-pression mediated via activation of the sterol regulatory element binding protein cleavage -activating protein/sterol regulatory element binding protein -2 pathway.Conclusion Interleukin -1βcan decrease the sensitivity of vascular smooth muscle cells to compactin.