| Atherosclerosis(AS)is a chronic inflammatory disease that occurs in the arteries throughout the body and is the pathological basis for cardiovascular diseases such as coronary heart disease and stroke.It leads to narrowing of the lumen,reduced blood flow,increased permeability,hardening of the vessel wall and the risk of blockage of the vessel when plaque is dislodged.The mechanisms of atherosclerosis are complex and there is no unified theory to explain its occurrence and development process.At present,there are no specific drugs for atherosclerosis,but lipid-lowering drugs are mostly used as adjunctive treatment.Burdock inulin(BFO)is a low molecular weight fructan with a molecular weight of 2000-5000 Da,extracted from the medicinal and food plant burdock.It has been reported that burdock inulin has lipid-regulating effects,and it is speculated that it may have some therapeutic effects on atherosclerosis.In this thesis,the effects of burdock inulin on atherosclerosis and its mechanism of action were investigated by constructing an in vitro foam cell model and a mouse model of atherosclerosis.I.Research on the effect of burdock inulin on in vitro models.A macrophage-derived foam cell model was induced using 50 μg/mL ox-LDL treatment of Raw264.7 macrophages for 24 h.ox-LDL induction modeling was accompanied by the administration of 250 μg/mL,500 μg/mL,and 1000 μg/mL BFO treatments.The results showed that,on the one hand,BFO inhibited the proliferative activity of foam cells,reduced the accumulation of intracellular lipids and attenuated the extent of macrophage foaminess.On the other hand,BFO also reduced the expression of NF-κB and iNOS mRNA,which are key regulators of pathological NO synthesis,and prevented the cellular damage caused by excessive NO.In addition,BFO also reduced the expression and synthesis of intracellular TNF-α and IL-1β,which alleviated the inflammatory response of the cells.2.Research on the effect of burdock inulin on in vivo models.A model of atherosclerosis was established in C57BL/6J mice fed high-fat,high-cholesterol,with a control group,a model group,a positive drug simvastatin group and a burdock inulin group,and the mice were dissected for 15 weeks.The results showed that BFO had no significant effect on the body weight of the model mice,and no significant difference in body weight was observed between the model,simvastatin and BFO groups.BFO reduced the serum levels of TC,LDL-C and ox-LDL,and the lipid levels converged to those of normal mice,reduced the atherosclerotic index and coronary heart index,and attenuated the degree of atherosclerosis in mice.Meanwhile,BFO burdock inulin reduced the levels of TNF-α,IL-1β,hs-CRP and MCP-1 in serum,and modulated the expression of TLR4,MyD88 and NF-κB in aorta and NF-κB and IL-1β mRNA in liver,resulting in a decrease in the level of inflammation in mice.In addition,BFO decreased the expression of CD36 mRNA,a key factor for hepatic lipid accumulation,and attenuated the expression of HMGCR and SREBP2 mRNA,the rate-limiting factors for hepatic cholesterol synthesis,and reduced the total hepatic cholesterol content.BFO increased the expression of ABCA1 in the aorta and LDLR mRNA in the liver,with enhanced cholesterol efflux from extrahepatic cells and liver uptake of LDL-C from blood vessels.BFO also activated the LXRα/ABCA1/CYP7A1 pathway,increasing the expression of CYP7A1 mRNA,and promoting the conversion of cholesterol into bile acids for excretion in the liver.In summary,BFO inhibited ox-LDL-induced foaming of Raw264.7 macrophages and showed significant preventive effects on atherosclerosis in a high-fat,high-cholesterol diet-induced C57BL/6J mouse model.BFO can play a role in combating atherosclerosis by regulating lipid homeostasis,reducing the level of inflammation in the body,and activating cholesterol reverse transport to maintain cholesterol metabolic homeostasis.This thesis provides a theoretical basis for the development of BFO as a drug and food for the prevention of atherosclerosis. |
