丹酚酸 B 通过下调 miR-146a 的表达抑制 Ang II 诱导的血管平滑肌细胞增殖及体内内膜增生。
Salvianolic acid B inhibits Ang II-induced VSMC proliferation in vitro and intimal hyperplasia in vivo by downregulating miR-146a expression.
机构信息
Department of Biochemistry and Molecular Biology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education of China, Hebei Medical University, Shijiazhuang, Hebei 050017, China.
Department of Neurology, the Second Hospital of Hebei Medical University, Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei 050000, China.
出版信息
Phytomedicine. 2019 May;58:152754. doi: 10.1016/j.phymed.2018.11.014. Epub 2018 Nov 12.
BACKGROUND
Salvianolic acid B (Sal B), a water-soluble compound extracted from Salvia miltiorrhiza that has been widely used to treat cardiovascular diseases for hundreds of years in China, exerts cardiovascular protection by multiple mechanisms. miR-146a is involved in vascular smooth muscle cell (VSMC) phenotypic modulation and proliferation. However, it has yet to be investigated whether the cardiovascular protective effect of Sal B is mediated by miR-146a.
PURPOSE
To determine the relationship among the cardiovascular protective effect of Sal B, miR-146a expression, and VSMC proliferation.
METHODS
MTS assay and cell counting were performed to evaluate the effect of Ang II, Sal B and miR-146a on VSMC proliferation. The neointima hyperplasia was assessed by hematoxylin/eosin staining. qRT-PCR was used to detect the expression of miR-146a, KLF5, cyclin D1 and PCNA. Western blot analysis was used to detect the expressions of KLF5, cyclin D1 and PCNA after miR-20b-5p was knocked down or overexpressed in VSMC.
RESULTS
Sal B suppressed intimal hyperplasia induced by carotid artery ligation and decreased Ang II-induced VSMC proliferation by down-regulating the positive cell-cycle regulators KLF5 and cyclin D1. Further experiments showed that VSMC proliferation and upregulation of KLF5 and cyclin D1 induced by Ang II were accompanied by elevated miR-146a level. Furthermore, overexpression of miR-146a promoted and knockdown of miR-146a reduced Ang II-induced VSMC proliferation and ameliorated intimal hyperplasia induced by carotid artery ligation. Sal B inhibited Ang II-induced VSMC proliferation by suppressing miR-146a expression.
CONCLUSION
Sal B inhibited Ang II-induced VSMC proliferation in vitro and intimal hyperplasia in vivo by downregulating miR-146a expression.
背景
丹酚酸 B（Sal B）是从丹参中提取的一种水溶性化合物，在中国已被广泛用于治疗心血管疾病数百年，通过多种机制发挥心血管保护作用。miR-146a 参与血管平滑肌细胞（VSMC）表型调节和增殖。然而，Sal B 的心血管保护作用是否通过 miR-146a 介导尚未得到研究。
目的
确定 Sal B 的心血管保护作用、miR-146a 表达与 VSMC 增殖之间的关系。
方法
采用 MTS 法和细胞计数法评价 Ang II、Sal B 和 miR-146a 对 VSMC 增殖的影响。通过苏木精/伊红染色评估新生内膜增生。采用 qRT-PCR 检测 miR-146a、KLF5、cyclin D1 和 PCNA 的表达。采用 Western blot 分析在 VSMC 中敲低或过表达 miR-20b-5p 后 KLF5、cyclin D1 和 PCNA 的表达。
结果
Sal B 抑制了颈动脉结扎引起的内膜增生，并通过下调阳性细胞周期调节因子 KLF5 和 cyclin D1 来减少 Ang II 诱导的 VSMC 增殖。进一步的实验表明，Ang II 诱导的 VSMC 增殖和 KLF5 和 cyclin D1 的上调伴随着 miR-146a 水平的升高。此外，过表达 miR-146a 促进了 Ang II 诱导的 VSMC 增殖，而敲低 miR-146a 则减少了 Ang II 诱导的 VSMC 增殖并改善了颈动脉结扎引起的内膜增生。Sal B 通过抑制 miR-146a 表达抑制了 Ang II 诱导的 VSMC 增殖。
结论
Sal B 通过下调 miR-146a 表达抑制了 Ang II 诱导的 VSMC 增殖，从而在体外和体内抑制了 Ang II 诱导的 VSMC 增殖和内膜增生。
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