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丹参酮 IIA 通过 klf4 介导的平滑肌细胞表型转换抑制血管重构。

Tanshinone II A attenuates vascular remodeling through klf4 mediated smooth muscle cell phenotypic switching.

机构信息

Chengdu University of Traditional Chinese Medicine, College of Basic Medicine, Chengdu, China.

Chengdu University of Traditional Chinese Medicine, College Pharmacy, Chengdu, China.

出版信息

Sci Rep. 2020 Aug 17;10(1):13858. doi: 10.1038/s41598-020-70887-1.

DOI:10.1038/s41598-020-70887-1
PMID:32807822
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7431534/
Abstract

The aim of this study is to investigate the therapeutic role of Tanshinone II A, a key integrant from salvia miltiorrhiza, against pathological vascular remodeling. Completed ligation of mouse left common carotid arteries animal model and rat smooth muscle cells used to investigate the role of Tanshinone II A in regulating pathological vascular remodeling through hematoxylin and eosin staining, immunohistochemistry staining, immunofluorescence staining, adenovirus infection, real time PCR and western blotting. Our data demonstrated that Tanshinone II A treatment suppresses vascular injury-induced neointima formation. In vitro studies on rat smooth muscle cell indicated that Tanshinone II A treatment attenuates PDGF-BB induced cell growth, and promotes smooth muscle cell differentiated marker genes expression that induced by rapamycin treatment. Tanshinone II A treatment significant inhibits rat smooth muscle cell proliferation and migration. Tanshinone II A promotes KLF4 expression during smooth muscle phenotypic switching. Overexpression of KLF4 exacerbates Tanshinone II A mediated smooth muscle cell growth inhibition. Tanshinone II A plays a pivotal role in regulating pathological vascular remodeling through KLF4 mediated smooth muscle cell phenotypic switching. This study demonstrated that Tanshinone II A is a potential therapeutic agent for vascular diseases.

摘要

本研究旨在探讨丹参酮 IIA(丹参的主要成分之一)在病理性血管重构中的治疗作用。通过对小鼠颈总动脉结扎模型和大鼠平滑肌细胞的研究,采用苏木精-伊红染色、免疫组织化学染色、免疫荧光染色、腺病毒感染、实时 PCR 和 Western blot 等方法,探讨丹参酮 IIA 调节病理性血管重构的作用。我们的数据表明,丹参酮 IIA 治疗可抑制血管损伤诱导的新生内膜形成。体外大鼠平滑肌细胞研究表明,丹参酮 IIA 治疗可减轻 PDGF-BB 诱导的细胞生长,并促进雷帕霉素诱导的平滑肌细胞分化标志物基因的表达。丹参酮 IIA 治疗可显著抑制大鼠平滑肌细胞的增殖和迁移。丹参酮 IIA 在平滑肌表型转换过程中促进 KLF4 的表达。过表达 KLF4 可加重丹参酮 IIA 介导的平滑肌细胞生长抑制。丹参酮 IIA 通过 KLF4 介导的平滑肌细胞表型转换在调节病理性血管重构中发挥关键作用。本研究表明,丹参酮 IIA 是一种治疗血管疾病的潜在药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e79d/7431534/0911a5830401/41598_2020_70887_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e79d/7431534/52d130b737c3/41598_2020_70887_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e79d/7431534/0a62f01db58e/41598_2020_70887_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e79d/7431534/d610a058ac68/41598_2020_70887_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e79d/7431534/6cc421855cdf/41598_2020_70887_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e79d/7431534/eb71d9cf9af5/41598_2020_70887_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e79d/7431534/0911a5830401/41598_2020_70887_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e79d/7431534/52d130b737c3/41598_2020_70887_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e79d/7431534/0a62f01db58e/41598_2020_70887_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e79d/7431534/d610a058ac68/41598_2020_70887_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e79d/7431534/6cc421855cdf/41598_2020_70887_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e79d/7431534/eb71d9cf9af5/41598_2020_70887_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e79d/7431534/0911a5830401/41598_2020_70887_Fig6_HTML.jpg

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Am J Transl Res. 2019 May 15;11(5):3140-3149. eCollection 2019.
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Tanshinone IIA attenuates ovalbumin-induced airway inflammation and hyperresponsiveness in a murine model of asthma.丹参酮IIA减轻卵清蛋白诱导的小鼠哮喘模型气道炎症和高反应性。
Iran J Basic Med Sci. 2019 Feb;22(2):160-165. doi: 10.22038/ijbms.2018.30598.7375.
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Tanshinone IIA inhibits AGEs-induced proliferation and migration of cultured vascular smooth muscle cells by suppressing ERK1/2 MAPK signaling.
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