Effect of Simiao Yongan Decoction on atherosclerotic carotid plaque in ApoE-/-mice via antagonizing Ox-LDL lipid metabolism pathway

摘要

Objective:To explore the intervention effects and mechanism of Simiao Yongan(SMYA)Decoction on carotid atherosclerotic plaque in ApoE knockout mice by antagonizing lipid metabolism of oxidation low density lipoprotein(Ox-LDL).Methods:ApoE-/-mice were fed high-fat feeding for 2 weeks,combined with perivascular collar placement(PCCP)and high fat feeding for 8 weeks to establish carotid AS plaque model.All the mouses were divided into 5 groups,after successful AS model preparation.The sham operation as well as model group intragastrically administered with deionized water.The rest mouses were intragastrically administered with SMYA decoction or Pioglitazone,or treated with Atorvastatin for 8 weeks.Then adopting automatic biochemical analyzer to test total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDL-C)content.The content of ox-LDL in serum,which was tested by enzyme-linked immunosorbent assay(ELISA).The pathological changes of carotid artery were observed by hematoxylin-eosin(HE)staining and the vascular parameters were measured.Immunohistochemical method and Western blot assay was used to detect the manifestations of protein include fatty acid binding protein 4(FABP4)and peroxisome proliferator-activated receptorγ(PPARγ)as well as matrix metalloproteinase 2(MMP 2).Results:Compared with the sham operation group,the serum ox-LDL content of the model group was increased,and the intima thickness(IT),intima-media thickness(IT/MT),plaque area(PA)as well as lumen area ratio of plaque vessels(PA/LA)were enlarged(P<0.05).Immunohistochemistry and Western blot results showed that the relative expression of FABP4 and MMP2 in the model group increased markedly,while the relative expression of PPARγsignificantly decreased.Compared SMYA decoction group and Atorvastatin group as well as Pioglitazone with model group,the serum ox-LDL content was decreased(P<0.05).In the mean time,the IT,PA,IT/MT and PA/LA in carotid artery were reduced(P<0.05).Immunohistochemistry and Western blot results showed that the expression of FABP4 and MMP2 was reduced,while PPARγprotein expression increased of mouses in each administration group.Conclusion:SMYA decoction is able to antagonize Ox-LDL,increase the expression of PPARγ,decrease the level of FABP4,reduce MMP2 in carotid arteries of ApoE-/-atherosclerotic mice,and increase the stability of plaque.