HSYA通过调控TGF-β1/Smad3通路抑制ANG诱导VAFs增殖  

HSYA inhibits the proliferation of ANGⅡinduced VAFs by regulating TGF-β1/Smad3 pathway

作　　者：崔清卓 许晴 李国婷 李颖云 刘博宇 安胜军 郑玉光[1] 赵京山[1,2,3] CUI Qingzhuo;XU Qing;LI Guoting;LI Yingyun;LIU Boyu;AN Shengjun;ZHENG Yuguang;ZHAO Jingshan(Traditional Chinese Medicine Processing Technology Innovation Center of Hebei Province,Hebei University of Traditional Chinese Medicine,Shijiazhuang 050200,China;College of Pharmacy,Hebei University of Traditional Chinese Medicine,Shijiazhuang 050200,China;International Joint Research Center on Resource Utilization and Quality Evaluation of Traditional Chinese Medicine of Hebei Province,Shijiazhuang 050200,China;Department of Science and Technology,Hebei University of Traditional Chinese Medicine,Shijiazhuang 050200,China)

机构地区：[1]河北中医学院河北省中药炮制技术创新中心,石家庄050200 [2]河北中医学院药学院,石家庄050200 [3]河北省中药资源利用与质量评价国际联合研究中心,石家庄050200 [4]河北中医学院科技处,石家庄050200

出　　处：《生命的化学》2022年第8期1552-1560,共9页Chemistry of Life

基　　金：河北省高等学校科学技术研究项目重点计划(ZD2017056);河北省自然科学基金项目(H2020423061);河北省中医药管理局科研计划项目(2017009);河北省大学、中学生在校科技创新能力培训计划项目(2021H011611,22E50140D);河北省重点研发计划项目中医药创新专项(223777149D)。

摘　　要：本研究旨在探究羟基红花黄色素A(hydroxysafflor yellow A,HSYA)是否通过调控TGF-β1/Smad3通路抑制血管紧张素Ⅱ(angiotensinⅡ,ANGⅡ)诱导血管外膜成纤维细胞(vascular adventitial fibroblasts,VAFs)增殖,从而抑制血管重构,缓解心血管疾病。采用组织贴块法培养SD大鼠VAFs;免疫荧光法鉴定VAFs;细胞随机分为正常组、ANGⅡ组、ANGⅡ+HSYA(低剂量、中剂量、高剂量)组;采用CCK-8法检测不同浓度HSYA对ANGⅡ诱导的VAFs增殖的作用;Western blot实验检测各组细胞中TGF-β1/Smads通路相关蛋白、各组细胞核蛋白p-Smad3的蛋白质表达。通过组织贴块法培养获得的细胞鉴定为VAFs;HSYA呈剂量依赖性抑制ANGⅡ诱导的VAFs增殖;降低了p-Smad3/Smad3蛋白表达,增加了Smad7蛋白表达;抑制了VAFs中核蛋白p-Smad3的蛋白质表达。HSYA通过调控TGF-β1/Smad3通路抑制Smad3磷酸化,增加Smad7蛋白表达,减少p-Smad3蛋白在细胞核内的含量,从而抑制ANGⅡ诱导的VAFs增殖,进而影响血管重构。To explore whether hydroxyl safflower yellow A(HSYA)inhibits the proliferation of ANGⅡinduced vascular adventitial fibroblasts(VAFs)by regulating TGF-β1/Smad3 pathway,then inhibits vascular remodeling and alleviating cardiovascular disease,VAFs in SD rats were obtained by tissue patch method.Immunofluorescence was used to identify VAFs.CCK-8 assay was used to detect the effect of different concentrations of HSYA on the proliferation of ANGⅡ-induced VAFs.The cells were randomly divided into normal group(NC),ANGⅡgroup(ANGⅡ),ANGⅡ+HSYA group(low,medium,and high-dose group).Western blot assay was used to detect the expression of TGF-β1/Smad3 pathway-related protein in total proteins and the expression of p-Smad3 in nuclear proteins.The results showed that the cultured cells were identified as VAFs.HSYA inhibited the proliferation of VAFs induced by ANGⅡ.HSYA decreased the expression of Smad3 and p-Smad3.HSYA increased Smad7 protein expression.HSYA inhibited p-Smad3protein expression in nucleus of VAFs.HSYA inhibits the proliferation of ANGⅡ-induced VAFs by regulating TGF-β1/Smad3 pathway,increasing Smad7 protein expression,and inhibiting p-Smad3 protein entry into the nucleus,then influences vascular remodeling.

关 键 词：羟基红花黄色素A 血管外膜成纤维细胞 细胞增殖 TGF-β1/Smad3信号通路 

分 类 号：R285.5[医药卫生—中药学]