Mechanism of Yiqi Tongmai Formula in Treatment of Atherosclerosis of Aorta in ApoE-/-Mice Based on TLR4/NF-κB Signaling Pathway
Objective To investigate the effect of Yiqi Tongmai Formula(YTF)on the inflammatory response of apolipoproteinE-/-(ApoE-/-)mice atherosclerosis(AS)based on the regulation of Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signalling pathway.Methods Forty male ApoE-/-mice were randomly divided into model group,the low,medium and high groups of YTF(0.39,0.78,1.56 g·kg-1·d-1),and the atorvastatin group(2.6 mg·kg-1·d-1),8 mice in each group,and 8 C57BL/6J mice of the same week of age as the blank control group.Except for the blank group,the AS model was induced by high fat diet.Each drug group was given the corresponding drug,and the blank group and model group were given the equal volume 0.9％sodium chloride solution for 12 consecutive weeks.The blood lipid level of mice was detected by enzyme marker assay;the expression of tumor necrosis factor-α(TNF-α)and monocyte chemotactic protein-1(MCP-1)in mouse serum were detected by ELISA;and the area of aortic plaque in mice was observed by oil red O staining;HE and Masson staining were used to observe the pathological changes of intima-media plaques in mouse aortic sinus;immunohistochemistry(IHC)and immunofluorescence(IF)methods were used to detect the expression of TLR4 and myeloid differentiation primary response protein88(MyD88)in aortic sinus;and Western Blot was used to detect the expression of TLR4/NF-κB signaling pathway-related factor protein in mouse aorta.Results Compared with the blank group,the serum levels of triglyceride(TG),total cholesterol(TC)and lowdensity lipoprotein cholesterol(LDL-C)significantly increased(P＜0.01),high-density lipoprotein cholesterol(HDL-C)levels significantly decreased in the model group(P＜0.01).Serum TNF-α,MCP-1 levels significantly increased(P＜0.01).The intima-media plaque as well as collagen fibres area in aortic sinus increased(P＜0.01),the protein expression of MyD88 increased(P＜0.01).The protein expression of aortic arch TLR4,NF-κB,nuclear factor κ B inhibitor alpha(IκBα),and MyD88 significantly increased(P＜0.01).Compared with the model group,the TC,TG and LDL-C levels in the medium and high dose groups of YTF and atorvastatin group significantly decreased(P＜0.01),the serum TNF-α and MCP-1 levels significantly decreased(P＜0.01),the aortic sinus plaques as well as the collagen fibres area increased(P＜0.01,P＜0.05),and the protein expression of aortic sinus,MyD88 significantly decreased(P＜0.01),and the protein expression of TLR4,NF-κB,MyD88,and IκB α in the aortic arch decreased(P＜0.01,P＜0.05).Conclusion YTF could improve the levels of blood lipids and inflammatory factors,and reduce lipid accumulation and foam cells in the aortic sinus,and its mechanism of action might be related to the down-regulation of TLR4/NF-κB signalling pathway.
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