The Inhibiting Effect And Possible Mechanisms Of Amygdalin On Atherosclerosis In LDL Receptor-deficient Mice

Objective:This study was aimed to investigating the inhibitory effect of amygdalin on atherosclerosis in LDL receptor-deficient mice,and to exploring potential mechanism of amygdalin inhibiting atherosclerosis in LDL receptor?deficient mice.This is to provide scientific basis for the development of amygdalin in clinical control of atherosclerosis.Method:(1)After establish the atherosclerotic model of LDL receptor?deficient mice,TC,TG,LDL-C and HDL-C in the serum of these mice were detected to study the effect of amygdalin on the lipid profile of LDL receptor?deficient mice.(2)The aim of oil red O staining and hematoxylin-eosin staining is to observe the pathological progression of amygdalin-regulated aortic sinus' s atherosclerosis plaque in LDL receptor?deficient mice.The effect of amygdalin on the progression of atherosclerosis in the aortic sinus of these mice was studied by evaluating aortic sinus lesion area,lumen area,plaque area,and aortic plaque coverage percentage.(3)Western blot analysis and RT-qPCR analysis were used to detect CD36,MCP-1,MMP-2,and MMP-9 in the spleen of LDL receptor?deficient mice after treatment with amygdalin.These are to investigate the regulatory effect of amygdalin on lipid infiltration and chemotactic inflammatory factors,and study the regulation of amygdalin on vascular endothelial extracellular matrix degradation and vascular remodeling.(4)The ELISA analysis was used to detect the IL-6 levels,IL-1? levels,and TNF-? levels in the serum of LDL receptor?deficient mice,and to evaluate the inhibitory effect of amygdalin on inflammatory factors in LDL receptor?deficient mice serum.Result:(1)Compared with LDL receptor?deficient control group mice,the serum TG,TC,and LDL levels of atherosclerosis mice were significantly reduced,and HDL-C levels were significantly increased after amygdalin treatment(respectively,P <0.05).(2)After amygdalin treatment(10 mg/kg),the oil red O staining results showed that the staining area was significantly reduced,and the lipid aggregation was effectively inhibited.The hematoxylin-eosin staining results showed that the size and number of plaques on the inner wall of the aorta of mice were effectively inhibited,the infiltrating inflammatory cells and fiber components were significantly reduced,no cholesterol crystals were observed.(3)The LDL receptor?deficient mice aortic sinus evaluation results showed that after amygdalin treatment,the aortic sinus lesion area,lumen area,and aortic plaque coverage percentage in LDL receptor?deficient mice were significantly reduced,and plaque area increased significantly(respectively,P <0.05).(4)After treatment with amygdalin,the protein expression levels and transcriptional abundance of CD36,MCP-1,MMP-2,and MMP-9 in the spleen of LDL receptor?deficient mice were significantly reduced(respectively,P <0.05).(5)After treatment with amygdalin,the serum inflammatory factors IL-6 levels,IL-1? levels,and TNF-? levels of LDL receptor?deficient mice were decreased significantly(respectively,P <0.05).Conclusion:(1)Amygdalin can effectively alleviate hypercholesterolemia in LDL receptor?deficient mice,and inhibit the formation of atherosclerotic plaques and vascular remodeling LDL receptor?deficient mice.(2)Amygdalin inhibits the expression of CD36,MCP-1,MMP-2,and MMP-9 in LDL receptor?deficient mice.(3)Amygdalin inhibits the expression of inflammatory factors IL-1?,IL-6 and TNF-? in LDL receptor?deficient mice.