| Objectives:The number of patients with atherosclerosis (AS) is rising quickly, which imply huge burden on the society and family. Atherosclerotic associated disease is the most common cause of mortality and morbidity of patients in developing and developed countries. AS is a chronic inflammatory process which refers to the damage endothelial cells, mononuclear macrophages,smooth musele cells, and amounts of cell factors and growth factors.Adhesion molecules, chemotatic factors and growth factors play important roles in the AS. The Traditional Chinese Medieine(TCM) has made certain achievements on the treatment of AS.TCM emphasizes much more on the adjustment of the whole function for the body,through the multi-ways, multi-links, and multi-targets comprehensive intervention. TCM surely has its potential treatment advantage to stable the vulnerable plaque. QiShenYiQi drop Pills (QSYQ drop Pills) made by TianshiLi Group has the effects of benefiting vital energy and promoting blood flow and has been used in cardiovascular system diseases with positive effects。 But the effects and mechanisms of QSYQ drop Pills is unknown. This study was carried out to observe the effects of QSYQ drop pills on established carotid atherosclerotic plaques in rats and explore the complex mechanisms.Methods:1. Establishment rat model of AS. A total of70male SD rats were divided into control group(n=7) and experiment group (n=63). The experiment group fed with high-cholesterol diet (1%cholesterol) continuously for16weeks,and was performed balloon catheter denudation of the endothelium in left common carotid artery used as a model of AS.Then the operated rats divided into Model+QSYQ drop Pills group,Model+Fluvastatin group,Model group,Sham group.2. Drug intervention, rats in Model+Q group were given QSYQ drop Pills (200mg/kg) by lavage administration. rats in Model+Q group were supplem-ented with Fluvastatin (5.5mg/kg).Model group、Sham group and Control group were given the same volume of distilled water. 3. Serological tests. Blood was drawn from angular vein of rats fasting overnight at baseline and at the end of weeks16and25. Serum levels of total cholesterol (TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C) and high-density cholesterol (HDL-C) were detected. The serum levels of interleukin-6(IL-6), tumor necrosis factor-α (TNF-a) and vascular cell adhesion molecule-1(VCAM-1)were measured by use of enzyme-linked immunosorbent assay(ELISA) at the end of weeks25.4. Histopathological analysis. Arteries were collected for paraffin sections. Paraffin sections were assessed by hematoxylin&eosin (H&E) and immunohistochemical staining. The carotid aretery intimal hyperplasia was identified by computer-Assisted image analysis system.Immunohistochemical staining was used to anal-yze the expression of inflammatory biomarkers.Transmission electron microscope were used to observe the ultrastructure of the carotid artery.Results1.Serological tests:①Lipid measurement:Serum levels of TC, TG and LDL-c at baseline in all rats have no significant differences (P>0.05). Serum levels of TC, TG, LDL-c were significantly elevated in high cholesterol diet rats for16weeks compared with the control group (P＜0.05). There was no differences between the high cholesterol groups(P＞0.05).Compared with the Model and Sham group,the levels of TC. LDL-c decreassed significantly in Model+Q and Model+F group (both P＜0.05) and the TC levels were lower in Model+F group than those in Model+Q group at25weeks. Inaddition, Model+Q decreased TG levels significantly(P＜0.05).②Inflammatory biomarkers:Compared with the Model group,the levels of IL-6. TNF-a and VCAM-1decreased significantly in Model+Q and Model+F group at25weeks.(both P＜0.05) and the IL-6levels were lower in Model+F group than those in Model+Q group at25weeks.2.Histopathological analysis:①Pathologic staining:The structure of the intima, the media and the adventitia of aortic wall was very clear.No thickening and no lipidoses were shown in the normal group rats. TheVSMCs in media were show a fusiform shape. The nucleus were stained in blue and arranged regularly as concentric circles. The thickened intima and foam cell aggregation were shown obviously in the model group.The arrangement of its VSMCs was disordered,and a large amount of nucleus was shown in the unit area.The intima was shown slightly thickened in the Model+Q and Model+F groups.The arrangement of their VSMCs was slightly disordered, and the amount of nucleus shown in the unit area in these two groups was smaller than that in the model group.②Immunohistoche-mical staining:The expressions of TNF-a and VCAM-1in plaques were lower in the two drug groups than those in the Model group.The expressions of TNF-a and VCAM-1were not apparent in Control group.③Electron microscopy examination:Transmission electron microscopy showed the structure of the intima and the media of carotid artery wall was very clear and no thickening and no lipidoses were shown in the Control group rats. The VSMCs were shown the fusiform shape with the presence of abundant myofilaments, normally arranged dense areas and dense bodies and a small quantity of mitochondria and endoplasmic reticulum in the normal rats. In the model group,the migration of VSMCs from media to endothelium was observed.The VSMCs appeared typical characteristics of synthetic phenotype, with depletion or decrease of myofilaments and swollen mitochondria. However,these changes were ameliorated when treated with QSYQ drop Pills or Fluvastatin.The mitochondria with slight swelling,dense areas,dense bodies and myofilaments were observed.In the Sham group, parts of the cell ultrastructure is disordered.Conclusions(1) The rats atherosclerosis model,which is established with balloon-induced carotid artery wall injury together with acholesterol-rich diet,is mimic to human atherosclerotic disease and suitable for the observation of drug therapeutic effects.(2) QSYQ drop pills and fluvastatin has an effect of anti-atherosclerosis by decreaseTC andLDL-c levels. The effect of fluvastatin about decreasing TC is better, and QSYQ drop pills is powerful to reduce the TG level. The combination of the two drugs might have better therapeutic effeets on blood lipids.(3) QSYQ drop pills and fluvastatin could stabilize the vulnerable plaque by decreasing the levels of blood inflammatory biomarkers and inhibiting the expression of them. |
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