摘要
丹参酮Ⅱa是我国传统中医药丹参的主要有效成分之一,已被广泛用于治疗多种心脑血管疾病。血管钙化是慢性肾病、糖尿病、高血压和动脉粥样硬化患者最常见的血管病理改变。然而,丹参酮Ⅱa是否抑制血管钙化尚不清楚。本研究采用血管平滑肌细胞和血管环钙化模型以及高剂量维生素D_(3)诱导的小鼠血管钙化模型,旨在探讨丹参酮Ⅱa抑制血管钙化的作用及其可能机制。茜素红染色和钙离子定量结果显示,丹参酮Ⅱa显著抑制高磷诱导的血管平滑肌细胞和血管环钙化。qPCR和Western blot结果表明丹参酮Ⅱa抑制血管平滑肌细胞向成骨样细胞转分化。丹参酮Ⅱa也显著抑制高剂量维生素D_(3)诱导的小鼠血管钙化和血管的成骨样转分化。机制研究显示,丹参酮Ⅱa抑制正常血管平滑肌细胞中NF-κB和β-catenin信号通路的激活。此外,与丹参酮Ⅱa类似,NF-κB和β-catenin特异性抑制剂SC75741和LF3也抑制高磷诱导的血管平滑肌细胞钙化。这些结果表明,丹参酮Ⅱa至少部分通过抑制NF-κB和β-catenin信号通路降低血管钙化的发生,提示丹参酮Ⅱa可能是治疗血管钙化的潜在药物。
TanshinoneⅡa is a key ingredient extracted from the traditional Chinese medicine Salvia miltiorrhiza(Danshen),and is widely used to treat various cardiovascular diseases.Vascular calcification is a common pathological change of cardiovascular tissues in patients with chronic kidney disease,diabetes,hypertension and atherosclerosis.However,whether TanshinoneⅡa inhibits vascular calcification and the underlying mechanisms remain largely unknown.This study aims to investigate whether TanshinoneⅡa can inhibit vascular calcification using high phosphate-induced vascular smooth muscle cell and aortic ring calcification model,and high dose vitamin D_(3)(vD_(3))-induced mouse models of vascular calcification.Alizarin red staining and calcium quantitative assay showed that TanshinoneⅡa significantly inhibited high phosphate-induced vascular smooth muscle cell and aortic ring calcification.qPCR and Western blot showed that TanshinoneⅡa attenuated the osteogenic transition of vascular smooth muscle cells.In addition,TanshinoneⅡa also significantly inhibited high dose vD_(3)-induced mouse aortic calcification and aortic osteogenic transition.Mechanistically,TanshinoneⅡa inhibited the activation of NF-κB andβ-catenin signaling in normal vascular smooth muscle cells.Similar to TanshinoneⅡa,inhibition of NF-κB andβ-catenin signaling using the chemical inhibitors SC75741 and LF3 attenuated high phosphate-induced vascular smooth muscle cell calcification.These results suggest that TanshinoneⅡa attenuates vascular calcification at least in part through inhibition of NF-κB andβ-catenin signaling,and TanshinoneⅡa may be a potential drug for the treatment of vascular calcification.
作者
钟慧
李带瑛
王苏樱
陈洁仪
陈佳欣
谭笑
王月恒
谢宇晨
朱东兴
ZHONG Hui;LI Dai-Ying;WANG Su-Ying;CHEN Jie-Yi;CHEN Jia-Xin;TAN Xiao;WANG Yue-Heng;XIE Yu-Chen;ZHU Dong-Xing(Biomedical Research Center,Basic Medical School,Guangzhou Medical University,Guangzhou 511436,China;School of Life Sciences,Guangzhou Medical University,Guangzhou 511436,China)
出处
《生理学报》
CAS
CSCD
北大核心
2022年第6期949-958,共10页
Acta Physiologica Sinica
基金
supported by the National Natural Science Foundation of China(No.82170428)
the‘Yangcheng Scholar’Grant of Guangzhou(No.202032768)to ZHU Dong-Xing
‘Climb Plan’Science and Technology Innovation Fund for The Undergraduate Students in Guangdong Province(No.pdjh2021b0418)to LI Dai-Ying
Research Training Grant for The Undergraduates of Guangzhou Medical University(No.S20211057058)to CHEN Jie-Yi
作者简介
通讯作者:朱东兴,博士,教授/博导,研究方向:心血管钙化是指磷酸钙盐在心血管组织中的异常沉积,其是糖尿病、动脉粥样硬化、高血压和慢性肾病等疾病患者普遍具有的共同血管病理表现。聚焦心血管钙化,通过细胞、动物模型和临床标本,采用高通量测序、生物信息学、分子生物学等先进技术手段,深入研究心血管钙化发病机制,旨在为心血管钙化的早期诊断和防治提供新的靶点。2017年回国后在广州医科大学基础医学院组建心血管钙化研究团队,先后担任副教授/教授,在心血管钙化领域取得了一定的研究成绩。目前已获得包括国家自然科学基金面上、青年基金,以及广东省自然科学基金在内的多项科研课题,课题组近年来的相关研究成果先后发表在Cardiovascular Research、Vascular Pharmacology、Trends in Biochemical Sciences、Journal of Biological Chemistry和Molecular and Cellular Endocrinology等知名杂志上,发表论文20余篇。担任广东省药理学会心血管专业委员会常务委员、广东省病理生理学会心血管专业委员会委员、Frontiers in Cardiovascular Medicine特邀编辑、Frontiers in Cell and Developmental Biology特邀副主编、《中国动脉硬化杂志》青年编委、国家自然科学基金委员会/广东省自然科学基金委员会通讯评审。Tel:+86-20-37103613,E-mail:dongxing.zhu@gzhmu.edu.cn;钟慧,These authors contributed equally to this work;李带瑛,These authors contributed equally to this work.
