四妙勇安汤调控滋养血管网重建稳定ApoE小鼠动脉粥样硬化易损斑块的实验研究

被引:28
作者
李萌 [1 ]
张军平 [1 ]
朱科 [2 ]
漆仲文 [2 ]
邹升 [2 ]
机构
[1] 天津中医药大学第一附属医院
[2] 天津中医药大学研究生院
关键词
滋养血管; 血管新生; 四妙勇安汤; HIF-1α-Apelin/APJ信号通路;
D O I
暂无
中图分类号
R285.5 [中药实验药理];
学科分类号
100806 [中药药理学];
摘要
观察四妙勇安汤干预AS易损斑块的效应,并以滋养血管(Vasa Vasorum,VV)新生为切入点,进一步探讨其起效的机制和靶点。方法:将雄性Apo E-/-小鼠随机分模型组、辛伐他汀组、四妙勇安汤组,采用添加1.1%L-蛋氨酸的高脂饲料喂养8周,建立AS易损斑块模型,并以C57BL/6小鼠作为对照。连续给药8周后,采用HE染色观察斑块的病理形态;采用免疫组化法观察斑块内与主动脉外膜VV密度以及斑块内巨噬细胞的聚集情况;检测血清TC、TG、LDL-C、HDL-C等血脂变化;采用Western blot技术检测HIF-1α-Apelin/APJ信号通路的关键节点蛋白。四妙勇安汤能够显著改善小鼠主动脉斑块病理形态,减小斑块面积及斑块与管腔面积比,增加最小纤维帽厚度以稳定斑块,且四妙勇安汤对纤维帽厚度的改善明显优于辛伐他汀;可有效抑制斑块内与血管外膜VV新生,降低斑块内巨噬细胞含量。四妙勇安汤可有效降低小鼠血清TC、TG、LDL-C水平,但对血清HDL-C水平无明显的改善作用。四妙勇安汤可降低HIF-1α蛋白表达水平,且其作用优于辛伐他汀;下调主动脉Apelin蛋白、APJ蛋白表达水平;显著降低Phospho-MEK1/2(Ser217/221)、Phospho-p44/42 MAPK(Erk1/2)(Thr202/Tyr204)、Phospho-p70 S6 Kinase(Thr421/Ser424)蛋白表达水平。结论:四妙勇安汤可通过调节HIF-1α-Apelin/APJ信号通路,抑制VV新生,从而稳定AS易损斑块。
引用
收藏
页码:1989 / 1997
页数:9
相关论文
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