Effects of Yiqi tongmai formula on atherosclerosis in ApoE-/-mice and its mechanism
OBJECTIVE To investigate the effects of Yiqi tongmai formula on atherosclerosis(AS)in ApoE-/-mice and its mechanism.METHODS Forty ApoE-/-mice were randomly divided into model group,positive control group[atorvastatin calcium,2.6 mg/(kg·d)],and low-dose,medium-dose and high-dose groups of Yiqi tongmai formula[0.46,0.91,1.82 g/(kg·d),by raw material],with 8 mice in each group.Eight C57BL/6J mice were selected as the normal group.Except for the normal group,the other groups were given a high-lipid diet and relevant drug or normal saline intragastrically,once a day,for 12 consecutive weeks.After the last medication,the serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)as well as the contents of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1β)and monocyte chemoattractant protein-1(MCP-1)were measured in mice.The proportion of aortic plaque area in each group of mice was detected and calculated,and the pathological morphological changes of the aortic sinus were observed;the protein phosphorylation levels of aortic phosphoinositide 3-kinase(PI3K),protein kinase B(aka Akt)and mammalian target of rapamycin(mTOR)were examined.RESULTS Compared with the model group,the serum levels of TC,TG and LDL-C and the contents of TNF-α,IL-1β and MCP-1(including low-dose group)were decreased significantly in medium-dose and high-dose groups of Yiqi tongmai formula,while the content of HDL-C in high-dose group was increased significantly(P＜0.05 or P＜0.01);aortic plaques of the mice were reduced in Yiqi tongmai formula groups to different extents,and pathological changes such as lipid deposition and inflammatory cell infiltration were relieved to different extents;the proportion of aortic plaque area,the protein phosphorylation levels of PI3K,Akt and mTOR in aortic tissue were significantly reduced in medium-dose and high-dose groups of Yiqi tongmai formula(P＜0.05 or P＜0.01).CONCLUSIONS Yiqi tongmai formula can improve lipid metabolism,reduce inflammatory response,and delay plaque development in AS mice.Its effect may be related to the inhibition of PI3K/Akt/mTOR signaling pathway activation.
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