| BackgroundAtherosclerosis (AS) is a very common and extremely important vascular disease. Nowadays, the prevention and treatment of atherosclerosis are becoming the focus of researchers due to its harmness to human’s living quality and health, rising morbidity and trend of younger age. How to intervene AS process actively and reduce the incidence of cardiovascular events has become the focus of modern medical research areas. The exsisting western medicine that can regulating lipid metabolism include platelet glycoprotein Ⅱb/Ⅲa receptor antagonists, cyclooxygenase inhibitors, antioxidants, calcium antagonists and etcetera. However, only statins is proved by large clinical trials, and it could not intervene integrately on AS because of its single active ingredient. Therefore, seeking ways to heal this disease from our precious traditional chinese medicine (TCM) is widely concerned by researchers and doctors. In recent years, positive explorations have been taken in the field of TCM treating and medicine to anti-atherosclerotic process. The current focus is primarily on activating blood, eliminating phlegm, detoxification, tonifying qi, etc. Activating blood and dissolving stasis herbs are still the mainstream. Single herb and Chinese patent medicine of many kinds are prove to be effective in relieving inflammation within AS plaques, protecting vascular endothelium, inhibiting plaque angiogenesis and matrix degradation in vitro and in vivo studies. But these studies have some questions that can not be ignored:Firstly, previous studies are many focused on advanced stage, and rare reports are of early intervention; Secondly, the animal model are not ideal, could not make a good simulation of AS mode; Lastly, evaluation indicators are outdated and lack of rigorous multi-center clinical studies and experimental comparative studies between western medicine in quality, targets features and advantages.Therefore, based on the thoery of "preventive treatment of disease", our experiment focus these questions above, using an activating blood and dissolving stasis based self-formula called "jia jian huo luo xiao ling dan (add-subtract HLXLD)" to intervene AS and plaques in ApoE-/-mice in early stage. We observe the atherosclerosis-related indicators, tissue lesions and inflammation in ApoE-/-mice, use PCR technique to test the expression of transforming growth factor-β(TGF-β), B scavenger receptor family of type I (SR-BI) and caveolin-1(Cav-1) in aorta to explain the formula’s function and mechanism and provide some ideas for further study and clinical treatment in atherosclerosis.ObjectivesTo explore the intervention and mechanism of atherosclerosis on ApoE-/-mice taking activating blood and dissolving stasis based formula add-subtract HLXLD through measuring arterial atherosclerosis plaque lesion, blood lipid metabolism, high-sensitivity C-reactive protein (H-CRP), transforming growth factor-β(TGF-β), B scavenger receptor family of type I (SR-BI) and caveolin-1(Cav-1).MethodsWe chose42male ApoE-/-mice, randomly divided them into3groups: model group (10), western medicine group (16) and TCM group (16). Three groups were fed high fat feed in order to establish atherosclerosis model. During this experiment, we daily give atorvastatin to western medicine group, add-subtract HLXLD (contains dansheng, sanqi, ruxiang, moyao) to TCM group, saline to model group according to weight ratio by gavage. The drugs used in this study were10fold to human.13weeks later, we measured total cholesterol (CHO), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), H-CRP in blood; TGF-β, SR-BI and Cav-1in aorta and calculated plaque, plaque/lumen area ratio.Results1. Content of serum CHO, TG, HDL-C, LDL-C in model group ApoE-/-mice increased after13weeks’high fat feed. Their aortic atherosclerosis and plaque formed.2. Compared with model group, the plaque area in add-subtract HLXLD group was significantly reduced.(P<0.01).3. Compared with model group, the expression of type I and type III fiber in add-subtraction HLXLD group was significantly reduced.4. Compared with model group, the H-CPR significantly reduced in add-subtraction HLXLD group (P=0.000)5. Compared with model group, the quantitative PCR results of add-subtraction HLXLD group showed that:the expression of TGF-β in ApoE-/- mouse aorta was significantly decreased (P<0.01), and the SR-BI expression was strongly increased (P<0.01). However, the Cav-1expression was no statistically significant difference (P>0.05).6. Compared with model group, mean of serum lipids in add-subtract HLXLD group significantly decreased (P<0.01).Conclusions1. High-fat fed for13weeks can successfully replicated atherosclerosis model in ApoE-/-mice.2. Add-subtraction HLXLD can lighten atherosclerotic wall damage, thicken plaque fibrous cap, reducing foam cells, macrophages, smooth muscle cell proliferation, extracellular and lipid deposition in the lesion area in ApoE-/-mice. Thus suggest add-subtraction HLXLD has good effert in anti-atherosclerosis, reduce plaque area and enhance plaque stability.3. The mechanisms of add-subtraction HLXLD’s anti-atherosclerotic function may be related to its function of reducing inflammation, inhibiting cell proliferation and spread and protecting endothelial cells by decreasing serum H-CRP, reducing aorta TGF-p expression and increasing SR-BI expressing.4. Add-subtraction HLXLD could regulate serum lipid metabolism. |
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