Study On The Molecular Mechanism With Zhixinkang On Atherosclerotic Vulnerable Plaque And Smooth Muscle-Derived Foam Cell

Objective: To discuss the molecular mechanism with zhixinkang on atherosclerotic vulnerable plaque and smooth muscle-derived foam cell, and provide scientific evidence for Zhixinkang development and clinical application. To study the opportunity of Zhixinkang as mimic PPARγexcitomotory, and discover the new target of traditional Chinese medicine(TCM) on atherosclerosis(As) treatment,and develop the research and application pathways of TCM on resist As.Methods: Through studying and analyzing the initial foundation and clinical application research of Zhixinkang, to combine with the latest advancement of TCM and Western medicine, and discuss the pathogenesis of As Vulnerable Plaque. 1. Animal experiment: 100 ApoE (-/-) mice of 6-week old were randomly assigned into five groups: A Zhixinkang group, B Xuezhikang group, C Lovastatin group, D Rosiglitazone group, E model group. Besides, a normal control group (Group F) was set up with 20 C57BL/6J mice. A-E groups were fed with Zhixinkang, Xuezhikang, Lovastatin, Rosiglitazone and Normal saline, F group were fed with Normal saline. After 12 weeks of intervention, to observe the effect on TC, TG, LDL-C, HDL-C and VLDL. TNF-αand IL-1βwere detected with ELISA method. To take aorta and observe pathomorphology, the expression of PPARγand ABCA1 were assayed by immunohistochemstry measurement. 2. Cell experiment: Vascular smooth muscle cells (VSMC) in aorta of SD rats were cultured, passaged and accredited. The cultured VSMC were loaded with ox-LDL to make foam cells. To assigned into five groups:A Zhixinkang group, B Xuezhikang group, C Lovastatin group, D Rosiglitazone group, E Normal saline group, and interfered with contain Zhixinkang serum, contain Xuezhikang serum, contain Lovastatin serum, contain Rosiglitazone serum, contain Normal saline serum. Group F was not interfered and as blank group. To detected cholesterin and cholesterl ester with high efficiency liquid chromatography, and Ca2+ of smooth muscle-derived foam cell with laser confocal microscopy, and CD36 mRNA expression with hybridization in situ.Results: 1. According to the theory integrated TCM and Western Medicine, to bring forward As vulnerable plaque pathogenesis of deficiency of qi, stagnation of blood and toxin, so propose a new therapeutic principle of supplementing qi activating blood and resolving toxin. It manifests that Zhixinkang is superior in treating As on the basis of initial foundation and clinical application research consequence. 2. Experiments shows (1) Zhixinkang could reduce blood lipid level of ApoE (-/-) mice; (2) Zhixinkang could reduce TNF-αand IL-1βlevel in ApoE (-/-) mice serum; (3) Zhixinkang could increace PPARγand ABCA1 level in ApoE (-/-) mice aorta, it is superior to Rosiglitazone; (4) Zhixinkang could restrain CD36 mRNA expression of smooth muscle-derived foam cell, it is superior to Lovastatin; (5) Zhixinkang could restrain Ca2+ concentration of smooth muscle-derived foam cell, it is superior to Lovastatin and Xuezhikang; (6) Zhixinkang has the effects for restraining smooth muscle-derived foam cell, anti-proliferation of VSMC, anti-As plaque formation, protecting configuration structure of aorta, and stabilizing plaque.Conclusion: Zhixinkang could excite PPARγ, regulate downstream target genes CD36, ABCA1 and correlated inflammatory factors TNF-αand IL-1β, restrain foam cell formation and blockade As course. Zhixinkang were anticipated to become a new and higher specificity PPARγexcitomotory of TCM, it could supplement qi activate blood and resolve toxin, which make toxin and turbidity in VSMC to resolve, restrain VSMC proliferation and foam cell formation. It could be one of the effective TCM in treating and preventing As, stabilizing As plaque.