香青兰总黄酮调控Notch1信号通路对ox-LDL诱导的血管平滑肌细胞表型转化的影响  

Effect of Dracocephalum Moldavica L.total flavonoids on phenotypic transformation of vascular smooth muscle cells induced by ox-LDL regulated by Notch1 signaling pathway

作　　者：岳茹婧 马晓莉[1,2] 郭新红 黄川生[1,2] 王新春[1,2] 曹文疆[2] YUE Rujing;MA Xiaoli;GUO Xinhong;HUANG Chuansheng;WANG Xinchun;CAO Wenjiang(Pharmacy of College,Shihezi University,Shihezi,Xinjiang 832002,China;First Affiliated Hospital of the Medical College,Shihezi University,Shihezi,Xinjiang 832008,China)

机构地区：[1]石河子大学药学院,新疆石河子832002 [2]石河子大学医学院第一附属医院,新疆石河子832008

出　　处：《石河子大学学报（自然科学版）》2021年第2期252-258,共7页Journal of Shihezi University(Natural Science)

基　　金：国家自然科学基金项目(81960766,81860747)。

摘　　要：目的研究香青兰总黄酮(TFDM)对大鼠血管平滑肌A7R5细胞表型转化的影响,探讨其用于动脉粥样硬化治疗的可能机制。方法实验分为6组,分组如下:ox-LDL刺激A7R5细胞表型转化作为模型组;用浓度分别为25、50、100μg·mL^(-1)TFDM处理表型转化的细胞作为低、中、高剂量组;10-5 mol·L^(-1)辛伐他汀处理表型转化的细胞,作为阳性对照组;未经处理的细胞作为正常对照组。采用CCK-8法测定细胞增殖,Transwell检测细胞迁移。蛋白免疫印迹测定SM22α,α-SMA和Notch1通路相关蛋白Notch1、actived-Notch1、RBP-Jκ、Hes-1及Hes-5蛋白的表达。结果与ox-LDL刺激的模型组比较,高剂量的TFDM刺激细胞后显著降低其增殖、迁移能力(P<0.001或P<0.05),上调SM22α,α-SMA表达(P<0.05),下调Notch1、actived-Notch1、RBP-Jκ、Hes-1及Hes-5的表达(P<0.001,P<0.01或P<0.05);中、低剂量的TFDM对细胞增殖、迁移及相关蛋白表达也有相应的调节,但作用不如高剂量显著。结论TFDM能显著抑制ox-LDL诱导A7R5细胞的过度增殖、迁移及表型转化,这种作用可能与调节了Notch1信号通路有关。Objective To investigate the effect of Dracocephalum Moldavica L.total flavonoids on phenotypic transformation of rat vascular smooth muscle A7R5 cells and explore the possible mechanism of TFDM in the treatment of atherosclerosis.Methods Cells were divided into 6 groups as follows:ox-LDL stimulated the phenotypic transformation of A7R5 cells as the model group;cells in TFDM-L,TFDM-M,TFDM-H groups were treated with TFDM at 25,50,100μg·mL^(-1)respectively;cells in Simvastatin group were stimulated by 10-5 mol·L^(-1)simvastatin after phenotypic transformation;untreated cells served as normal control group.Cell proliferation was tested by CCK-8 assay and cell migration was measured by Transwell assay.Western blot was performed to determine the protein expression of SM22α,α-SMA,Notch1,actived-Notch1,RBP-Jκ,Hes-1,and Hes-5.Results Compared with model group,TFDM-H significantly reduced cell proliferation and migration(P<0.001 or P<0.05),the expression of SM22αandα-SMA(P<0.05),down-regulated expression of Notch1,actived-Notch1,RBP-Jκ,Hes-1,and Hes-5(P<0.001,P<0.01 or P<0.05);Medium and low doses of TFDM also had corresponding regulation on cell proliferation,migration and related protein expression,but the effect was not as significant as that of high doses.Conclusion TFDM can significantly inhibit ox-LDL induced excessive proliferation,migration,and phenotypic transformation of A7R5 cells,which is related to the regulation of Notch1 signaling pathway.

关 键 词：香青兰总黄酮 动脉粥样硬化 血管平滑肌细胞表型转化 NOTCH1 

分 类 号：R285.5[医药卫生—中药学]