Research On Effects Of Tong Mai Di Xian Pill To Angiogenesis In Atherosclerotic Plaque And Plaque Stability

Atherosclerosis (As) is the important pathology foundation of cardiovascular and cerebrovascular diseases. It mainly occurred in the large and medium-sized arteries, especially the coronary arteries, cerebral arteries and aorta. Coronary heart disease and stroke are the major complications of As, which is a major cause of death in the worldwide. Therefore, it is the primary goal of treating cardiovascular and cerebrovascular diseases in clinical, that the process of As and its complications should be controlled. Recent researches found, pathological neovascularization occurred in atherosclerotic plaque, which can promoting the development of As, even causing the occurrence of plaque rupture and its complications. So inhibiting the angiogenesis in the plaque will probably enhance stability in the plaque, and may even make the plaque regression, which to achieve reducing the generation of cardiovascular and cerebrovascular diseases in clinical.Traditional Chinese medicine (TCM) suggests that the etiology and pathogenesis are improper diet, overstrain and internal injury, senility or body deficiency catching exogenous evil, leading to stagnation of qi, turbid phlegm, blood stasis, which accumulate with each other to block meridians and which induce the deficiency in origin and excess in superficiality syndrome. The pathological neovascularization occurred in atherosclerotic plaque belongs to collateral disease in TCM at present, which is associated with that the body of collaterals and vessels of collaterals are hyperplasia without making, hyperactivity causing damage, results in the inordinate state of collateral internal environment. There are advantages of long-term use of TCM treating As, which are safe and curative effect stable. In many intervention studies of using TCM to treat the angiogenesis in atherosclerotic plaque, it shows that the TCM can inhibit the angiogenesis occurred in atherosclerotic plaque effectively, so as to delay the process of As, and to reverse the hyperplasia of plaque, even to cure the plaque, and then to achieve the goal of preventing and treating As.My tutor, Professor Luo Luyi considers that the deficiency of kidney qi, phlegm-stasis blocking collaterals is an important pathogenesis of the formation of As and its plaque. Acorrding to his clinical research for many years and combining with modern scientific research materials, Professor Luo developed the compound traditional Chinese medicine preparation Tong mai Di xian Pill, which has many functions such as invigorating the kidney, activating blood, resolving phlegm and so on. Tong mai Di xian Pill made in our hospital also has the significant functions in antioxidation, vasodilative effect, improving circulation, which is widely used in clinical for treating the As diseases like coronary heart disease, cerebral infarction and so on, and it has obtained a satisfactory effect.For further research on the mechanism of Tong mai Di xian Pill preventing and treating As in occurrence and development, this research subject starts from studying on the angiogenesis in atherosclerostic plaque, and we summarized the research progress of angiogenesis in atherosclerostic plaque studied by TCM and western medicine, by the clinical trial and the animal experiment study, the angiogenesis of astherosclerostic plaque and its related indexes were detected, so as to study on the mechanism of Tong mai Di xian Pill controlling the progress of As, and even reducing the plaque.1 Clinical trial:Study on effects of Tong mai Di xian Pill treating the patients of carotid atherosclerosis (CAS)1.1 Objective:To research the mechanism that Tong mai Di xian Pill improving the general TCM symptoms of CAS patients and making the plaque stable, and the serum level of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2) were detected in CAS patients treated by Tong mai Di xian Pill.1.2 Methods:According to the case selection standard,98 CAS patients were observed in herbal treatment group (HTG) and statins treatment group (STG),48 patients in either group. HTG gived Tong mai Di xian Pill to patients by mouth, and STG gived Atorvastatin calcium, which were used for 6 months. The indexes are detected, that are the carotid artery ultrasound, plaque score, lipid level, TCM syndrome score, total curative effect of TCM symptoms and serum level of VEGF, FGF-2.1.3 Results:Compared with before treatment, the TCM symptom and indexes in two groups got better obviously; in some aspects, the HTG was superior to the STG, such as the total curative effect of TCM symptoms, TCM syndrome score, serious extent, regressing and reducing the soft plaque number of carotid plaque, lowering the resistance index (RI) in internal carotid artery (ICA) and bifurcation (BIF), improving the pulsatility index (PI) in external carotid artery (ECA) and ameliorating the serum level of VEGF and so on.1.4 Conclusions:Using Tong mai Di xian Pill can ameliorate the CAS patients symptoms, which can reduce and decrease the soft plaque, and improve the indexes of carotid artery ultrasound, and then delay the progress of As.2 Animal experiment study:The mechanism and effects of Tong mai Di xian Pill on the angiogenesis of atherosclerostic plaque in As model rabbits2.1 Objective:To research the mechanisms that Tong mai Di xian Pill affects As and its angiogenesis in plaque, and the mechanisms that Tong mai Di xian Pill makes the plaque stable and even reduces the plaque.2.2 Methods:40 male rabbits were divided into four groups at random:normal group(NG), model group (MG), HTG and STG, and 10 rabbits in each group. At the beginning, each group except NG were fed on high fat diet, and were injected bovine serum albumin (BSA) through the ear vein, to make into As model. After 10 weeks, the formation of As was observed, and the successful symbol of As was aortic plaques occurred. It is time to change normal diet to feed MG, HTG, STG rabbits. There was only feeding of NG without intervention, while both HTG and STG were administrated by gastric perfusion of medicine until the end of experiment, and MG were administrated by gastric perfusion of normal saline. Analyze the serum lipid level of every group before and after the experiment, and observe the internal structure of plaque and the expression of CD34, VEGF, FGF-2 in plaque, which were the marker and important factors of angiogenesis. Both the positive staining area rate of CD34, VEGF and the average optical density of FGF-2 were observed and calculated. Observe the internal expression structure of plaque inhematoxylin-eosin (HE) staining and immunohistochemical staining, and the internal cellular structure of plaque through the electron microscope.2.3 Results:The various serum level of lipid of MG increased significantly compared with NG. The level of both TC and LDLC were decreased effectively in HTG and STG, and the STG was superior to the HTG in the level of TC, while the HTG was superior to the STG in the level of LDLC. Tong mai Di xian Pill was effective with the level of HDLC. No matter the expression observed in gross specimen or HE staining or immunohistochemical staining or through the electron microscope, the expression was significantly on improving AS plaque both in the HTG and the STG. Both treatments can ameliorate the expression of positive staining area of CD34 in the plaque, so that it can get the area of angiogenesis better. In addition, Tong mai Di xian Pill can ameliorate the expression of positive area of VEGF in the plaque, and there is no effect in the positive expression of FGF-2 in both treatments.2.4 Conclusions:The As animal model in the experiment is successful, and the serum lipid level is significantly increased. Both Tong mai Di xian Pill and Atorvastatin calcium can ameliorate the serum lipid level of As and the area of angiogenesis in the plaque effectively. The Tong mai Di xian Pill is superior to the Atorvastatin calcaium obviously in the aspects of ameliorating angiogenesis area and getting the plaque regressed. It is obviously effect that the application of Tong mai Di xian Pill makes the plaque of As decrease or regression, therefore it can attain to purpose of delaying the process of As disease.