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司妙勇安通过促进血管外膜血管成熟和稳定载脂蛋白 E 基因敲除小鼠动脉粥样硬化斑块的作用:一项实验研究。

Si-Miao-Yong-An on promoting the maturation of Vasa Vasorum and stabilizing atherosclerotic plaque in ApoE mice: An experimental study.

机构信息

First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300183, China.

First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300183, China.

出版信息

Biomed Pharmacother. 2019 Jun;114:108785. doi: 10.1016/j.biopha.2019.108785. Epub 2019 Mar 23.

DOI:10.1016/j.biopha.2019.108785
PMID:30909142
Abstract

OBJECTIVE

To observe the intervention effect of Si-miao-Yong-An (SMYA) on atheroosclerosis (AS) vulnerable plaque, and to explore the mechanism by Vasa Vasorum (VV) maturation as a starting point.

MATERIALS AND METHODS

SPF-class healthy male ApoE mice were randomly divided into model group, SMYA group and simvastatin group, and C57BL/6 mice were used as a control group. After 8 weeks of drug intervention, the plaques of AS were observed by HE staining. The pericytes of aortic root plaques were observed by immunofiuorescence double staining (CD34, Desmin) and the density of VV. The expression of Dll4, Notch1, Hey1 and VEGF mRNA in aortic tissues was detected by real-time qPCR.

RESULTS

SMYA significantly reduced the area of aortic plaque in ApoE mice, significantly reduced plaque area and the ratio of plaque to lumen area, and reduced the intima medium thickness, it's effect was greater than that of simvastatin; it significantly increased the density of VV in plaque. SMYA increased the expression of Dll4 and Notch1 and Hey1mRNA, and decreased the expression of VEGF mRNA, and its effect was greater than that of simvastatin.

CONCLUSION

SMYA can reduce the AS plaque area in ApoE mice, promote the recruitment of VV pericytes, and stabilize AS vulnerable plaques. The mechanism may be regulate of Dll4/Notch1/ Hey1/VEGF signaling pathway. At the same time, it has a dual-direction regulation on the VV.

摘要

目的

观察四妙勇安方干预动脉粥样硬化(AS)易损斑块的作用,并以血管新生(VV)成熟为切入点探讨其作用机制。

材料与方法

选取 SPF 级健康雄性 ApoE 小鼠随机分为模型组、四妙勇安方组和辛伐他汀组,以 C57BL/6 小鼠作为空白对照组。药物干预 8 周后,行 HE 染色观察 AS 斑块,免疫荧光双染(CD34、Desmin)观察主动脉根部斑块周细胞及 VV 密度,实时 qPCR 检测主动脉组织中 Dll4、Notch1、Hey1、VEGF mRNA 的表达。

结果

四妙勇安方能显著减少 ApoE 小鼠主动脉斑块面积,显著减少斑块面积和斑块面积与管腔面积比值,降低内膜中层厚度,其作用强于辛伐他汀;能显著增加斑块中 VV 密度。四妙勇安方上调 Dll4、Notch1、Hey1mRNA 的表达,下调 VEGF mRNA 的表达,其作用强于辛伐他汀。

结论

四妙勇安方能减少 ApoE 小鼠 AS 斑块面积,促进 VV 周细胞募集,稳定 AS 易损斑块,其作用机制可能与调控 Dll4/Notch1/Hey1/VEGF 信号通路有关。同时,其对 VV 具有双向调节作用。

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