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蚤休薯蓣皂苷对内皮细胞的保护作用涉及TLR4/NF-κB途径 被引量:13

Effect of rhizome saponins on TLR4 signal transduction pathways on ox-LDL damaged human endothelial cells
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摘要 目的观察蚤休薯蓣皂苷(Rhizome Dioscin,RD)对氧化性低密度脂蛋白(ox-LDL)诱导人脐静脉内皮细胞(HU-VEC)损伤对细胞生长、炎症反应Toll样受体4(TLR4)和细胞核因子κB(nuclear factor kappa B,NF-κB)表达的影响,探讨RD抗动脉粥样硬化(AS)的作用机制。方法体外培养HUVEC,RD 3个浓度预处理,加入ox-LDL,运用流式细胞术PI染色检测细胞周期,激光共聚焦显微镜JC-1染色检测线粒体电位(ΔΨm),Western blot检测TLR4和NF-κB蛋白的表达。结果与正常对照组相比,经ox-LDL损伤后HU-VEC细胞周期阻滞在G0/G1期,表现为G0/G1期细胞比例明显升高(P<0.01),S期细胞比例明显下降(P<0.01);细胞ΔΨm明显下降;TLR4和NF-κB的表达与正常组比较均升高。RD预处理能抑制ox-LDL诱导的细胞生长停滞,使细胞周期S期细胞比例增加(P<0.01),ΔΨm上升,TLR4和NF-κB的表达与损伤组相比均下降。结论抑制TLR4/NF-κB信号转导途径可能是RD抗内皮细胞氧化损伤、阻止经线粒体途径的细胞生长停滞的可能机制之一。 Aim To observe the effect of Rhizome Di-oscin(RD)on cell growth,Toll like receptor 4(TLR4) and the nuclear factor kappa B(NF-κB)signal transduction pathways on human umbilical vein endothelial cells HUVEC damaged by oxidizing low density lipoprotein(ox-LDL),and to discuss the anti-atherosclerosis(AS)mechanism of the RD.Methods Three concentration RD pretreated,HUVEC cultured in vitro,flow cytometry was used to detect cell cycle.Laser scanning confocal microscope JC-1 dyeing to detect mitochondria membrane potential(ΔΨm)and western blot to test TLR4 and the NF-κB protein expression. Results Cell cycle in ox-LDL injured group was blocked in G 0 / G 1 phase and cell number of G 0 / G 1 phase was increased(P 0.01)but cell number of S phase was decreased(P 0.01).The mitochondrial membrane potential was obviously decreased,expression of TLR4 and the NF-κB in injured group were increased compared with normal control.RD group could block cell growth stagnation induced by ox-LDL,make the cell number of G 0 / G 1 phase decrease and S phase increase in the meantime(P 0.01),ΔΨm rose. TLR4 and NF-κB expression were decreased compared with injured control.Conclusion RD can inhibit TLR4 / NF-κB signal transduction pathway on HUVEC, restrain the mitochondrial oxidative damage by the way of cell growth stagnation and this may be one of the possible mechanisms of anti-AS of RD.
出处 《中国药理学通报》 CAS CSCD 北大核心 2012年第11期1598-1602,共5页 Chinese Pharmacological Bulletin
基金 山东省自然科学基金资助项目(No ZR2011HL014) 山东省高等学校科技计划项目(No J10LF18)
关键词 蚤休薯蓣皂苷 氧化性低密度脂蛋白 内皮细胞 细胞周期 线粒体膜电位 Toll样受体4 细胞核因子ΚB Rhizome Dioscin oxidizing low density lipoprotein human endothelial cells cell cycle mitochondrial membrane potential Toll like receptor 4 the nuclear factor kappa B
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