基于调控ABCA1表达探讨升麻苷抗动脉粥样硬化的作用机制  

Anti-atherosclerosis mechanism of cimicifugoside by regulation of ABCA1 expression

作　　者：王仙伟[1] 雷虹 何欣威 朱峰[1] 柯绍发[1] WANG Xian-wei;LEI Hong;HE Xin-wei;ZHU-feng;KE Shao-fa(Zhejiang Provincial Taizhou Hospital,Taizhou 318000,China;Zhejiang Taizhou Institute for Food and Drug Control,Taizhou 318000,China)

机构地区：[1]浙江省台州医院神经内科,台州318000 [2]浙江省台州市食品药品检验研究院,台州318000

出　　处：《浙江中西医结合杂志》2021年第11期990-994,共5页Zhejiang Journal of Integrated Traditional Chinese and Western Medicine

基　　金：浙江省台州市科技局项目(No.1701KY15)。

摘　　要：目的研究升麻苷对人单核细胞THP-1源性巨噬泡沫细胞炎症因子白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的影响,调控腺嘌呤核苷三磷酸结合盒转运体A1(ABCA1)表达,探讨其抗动脉粥样硬化的机制。方法使用适当浓度升麻苷(16、64μg/mL)作用于诱导成功的THP-1源性巨噬泡沫细胞,ELISA法测定细胞上清培养液IL-6、TNF-α表达,Western blot测定IL-6、TNF-α以及ABCA1的蛋白表达量,闪烁计数法测定细胞内胆固醇流出率。结果与对照组比较,升麻苷干预浓度128、256μg/mL对泡沫细胞呈现损伤[(90.29±5.46)%、(66.02±4.11)%比(100.22±3.13)%,P<0.05或P<0.01];与对照组比较,模型组泡沫细胞上清液IL-6、TNF-α含量明显增加[(58.93±8.34)pg/mL比(27.86±7.53)pg/mL,P<0.01;(208.76±9.07)pg/mL比(89.35±8.15)pg/mL,P<0.01],细胞IL-6、TNF-α蛋白表达明显增加[(0.89±0.09)比(0.32±0.05),P<0.01;(1.78±0.21)比(1.13±0.12),P<0.01],ACBA1蛋白表达降低[(1.11±0.12)比(1.74±0.13),P<0.01],胆固醇流出率增加[(15.32±0.72)%比(9.13±1.06)%,P<0.01]。与ox-LDL模型组比较,16、64μg/mL升麻苷能明显减少上清液IL-6、TNF-α含量[(47.71±9.38)pg/mL、(41.24±7.69)pg/mL比(58.93±8.34)pg/mL,P<0.05或P<0.01;(188.74±7.09)pg/mL、(107.95±8.23)pg/mL比(208.76±9.07)pg/mL,P<0.05或P<0.01],减少IL-6、TNF-α蛋白表达[(0.76±0.08)、(0.60±0.07)比(0.89±0.09),P<0.05或P<0.01;(1.61±0.14)、(1.29±0.18)比(1.78±0.21),P<0.05或P<0.01],增加ACBA1蛋白表达[(1.25±0.16)、(1.60±0.14)比(1.11±0.12),P<0.05或P<0.01],增加胆固醇流出率[(17.26±0.85)%、(20.23±1.98)%比(15.32±0.72)%,P<0.05或P<0.01]。结论升麻苷可能通过抑制THP-1源性巨噬泡沫细胞炎症因子IL-6、TNF-α表达,提升ABCA1表达,促进胆固醇外排,从而发挥抗炎及抑制动脉粥样硬化作用。Objective To assess the effect of Cimicifugoside on the expression of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in human monocyte THP-1-derived macrophage foam cells and the underlying molecular events.Methods The THP-1 cells were treated with or without oxidized low-density lipoprotein(ox-LDL group and control group)and then with or without Cimicifugoside(16,64μg/mL).Cells were subjected to Western blot and/or ELISA analyses of IL-6,TNF-α,and ABCA1 proteins.The intracellular cholesterol efflux was assayed using the liquid-scintillation counting.Results Cell viability was reduced after treated with 128 and 256μg/mL of Cimicifugoside compared with that of control cells(90.29±5.46 and 66.02±4.11 vs.100.22±3.13,respectively;P<0.05 and P<0.01).Compared with the control cells,levels of IL-6 and TNF-αin the cell culture supernatant(58.93±8.34 vs.27.86±7.53pg/mL;P<0.01 and 208.76±9.07 vs.89.35±8.15pg/mL;P<0.01),expression of IL-6 and TNF-αproteins(0.89±0.09 vs.0.32±0.05;P<0.01 and 1.78±0.21 vs.1.13±0.12;P<0.01)and ACBA1 expression was significantly reduced(1.11±0.12 vs.1.74±0.13;P<0.01).the cholesterol efflux rate(15.32±0.72 vs.9.13±1.06;P<0.01)were significantly increased in the ox-LDL group.In contrast.Compared with the ox-LDL model group,16 and 64μg/mL of Cimicifugoside treatment significantly reduced IL-6 and TNF-αlevels in the supernatant(47.71±9.38 and 41.24±7.69 vs.58.93±8.34pg/mL;P<0.05 and P<0.01;188.74±7.09 and 107.95±8.23 vs.208.76±9.07pg/mL;P<0.05 and P<0.01)and the cell expression of IL-6 and TNF-αproteins(0.76±0.08 and 0.60±0.07 vs.0.89±0.09;P<0.05 and P<0.01;and 1.61±0.14 and 1.29±0.18 vs.1.78±0.21;P<0.05 and P<0.01).However,expression of ACBA1 protein was increased(1.25±0.16 and 1.60±0.14 vs.1.11±0.12;P<0.05 and P<0.01)and the cholesterol efflux rate was also significantly increased(17.26±0.85 and 20.23±1.98 vs.15.32±0.72;P<0.05 and P<0.01).Conclusion Cimicifugoside reduces level of inflammatory factors IL-6 and TNF-αin THP-1-derived foam cell by enh

关 键 词：动脉粥样硬化 升麻苷 炎症因子 胆固醇转运 

分 类 号：R285[医药卫生—中药学]