6-姜烯酚通过下调TLR4/NF-κB通路抑制血管平滑肌细胞增殖  

6-shogaol suppresses vascular smooth muscle cells proliferation by inhibiting TLR4/NF-κB signaling pathway

作　　者：陈磊[1] 胡子成[1] 周毅[1] 张明杰[1] 王旭[1] 皮燕[1] 龙春燕[1] 孙梦娇[1] 陈雪[1] 李敬诚[1] 张莉莉[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所神经内科,重庆400042

出　　处：《第三军医大学学报》2016年第3期245-250,共6页Journal of Third Military Medical University

基　　金：国家自然科学基金面上项目(81271282;81471193;81400967)~~

摘　　要：目的探讨6-姜烯酚对血管平滑肌细胞(vascular smooth muscle cells,VSMCs)增殖的影响及其可能的分子机制。方法组织贴块法培养野生型(wild type,WT)和Toll样受体4敲除(Toll-like receptor 4 knockout,TLR4^(-/-))小鼠原代VSMCs。应用血小板源性生长因子(platelet derived growth factor,PDGF)诱导VSMCs增殖。分别应用TLR4配体脂多糖(LPS)和TLR4抑制剂(Eritoran,E5564)激活和抑制TLR4,观察TLR4在VSMCs增殖中的作用。加入6-姜烯酚刺激,观察对VSMCs增殖以及对TLR4表达的影响。结果 6-姜烯酚呈浓度依赖性地抑制PDGF诱导的VSMCs增殖(P<0.05);PDGF和LPS均可激活TLR4并促进野生VSMCs的增殖(P<0.05),TLR4基因敲除抑制PDGF和LPS诱导的VSMCs增殖(P<0.05);6-姜烯酚下调VSMCs中TLR4表达(P<0.05)。6-姜烯酚下调VSMCs中TLR4下游蛋白NF-κB的表达(P<0.05)。结论 6-姜烯酚通过下调TLR4/NF-κB通路抑制血管平滑肌细胞增殖。Objective To determine the effect of 6-shogaol on the proliferation in vascular smooth muscle cells（ VSMCs） and investigate its underlying mechanism. Methods VSMCs were isolated from the thoracic aorta of wild-type（ WT,C57 BL /6J background） and Toll-like receptor 4 knockout（ TLR4-（- /-）,C57 BL /6J background） mice. Platelet derived growth factor（ PDGF） was used to induce the proliferation in the obtained VSMCs. In order to observe the effect of TLR4 in VSMCs,LPS was added to the medium of TLR4- /-and WT VSMCs respectively to activate TLR4,while TLR4 inhibitor,E5564 was used to inhibit the expression of TLR4. 6-shogaol was added to observe its effect on the proliferation and TLR4 expression in VSMCs. Results 6-shogaol inhibited the proliferation of VSMCs in a dose-dependent manner（ P〈0. 05）.Both PDGF and LPS activated TLR4 and promoted the cell proliferation（ P〈0. 05）,but knockout of TLR4 gene suppressed the induced proliferation（ P〈0. 05）. 6-shogaol also inhabited the expression of TLR4 and its downstream protein,NF-κB（ P〈0. 05）. Conclusion 6-shogaol suppresses the proliferation in VSMCs via inhibiting TLR4/NF-κB signaling pathway.

关 键 词：血管平滑肌细胞 细胞增殖 6-姜烯酚 TLR4 

分 类 号：R282.71[医药卫生—中药学] R322.12[医药卫生—中医学]