Experimental Study of Si-Miao Yong-An Decoction Regulating Vasa Vasorum Remodeling in ApoE-/-Mice with Atherosclerosis Vulnerable Plague / 世界科学技术-中医药现代化

ABSTRACT

This study was aimed to observe the effect of Si-Miao Yong-An (SMYA) decoction intervention in atherosclerosis (AS) vulnerable plaque,and to further explore the action mechanism from the entry point of vasa vasorum (VV) neovascularization.Male ApoE-/-mice were randomly divided into the model group,simvastatin group and SMYA group.High-fat diet added 1.1％ L-methionine was fed for 8 weeks to establish the AS vulnerable plaque model.The C57BL/6 mice were used as control.After 8 weeks' continuous medication,mice were sacrificed.HE staining were used to observe the pathological changes of mice aorta;immunohistochemical staining was used to observe the VV density in AS plaque and aortic adventitia;macrophage infiltration in plaque was also detected;the blood-lipid changes of TC,TG,LDL-C and HDL-C were detected;western blot was used to detect essential proteins of HIF-1α-Apelin/APJ signal pathway.The results showed that SMYA decoction decreased the plaque area and the ratio of plaque area and lumen area,increased the minimum thickness of fibrous cap,which significantly improved the pathological feature of aortic plaque in mice.The function of increasing the minimum thickness of fibrous cap was obviously superior to simvastatin.SMYA decoction effectively suppressed the VV neovascularization and decreased the macrophage content.SMYA decoction effectively decreased the serum level of TC,TG and LDL-C;however,it had no effect on HDL-C.SMYA decoction decreased the protein expression of HIF-1α.Its function was obviously superior to simvastatin.SMYA decoction can down-regulate the protein expressions of Apelin,APJ,Phospho-MEK1/2 (Ser217/221),Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204) and Phospho-p70 S6 Kinase (Thr421/Ser424).It was concluded that SMYA decoction regulated the HIF-1α-Apelin/APJ signal pathway,suppressed VV neovascularization and stabilized AS vulnerable plaque.