通脉地仙丸对动脉粥样硬化斑块内血管新生及其稳定性影响的研究
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摘要
动脉粥样硬化(atherosclerosis, As)是心脑血管疾病的重要病理学基础,主要发生在大及中等动脉,特别是冠状动脉、脑动脉和主动脉。冠心病和中风是As的两大主要并发症,是危害人类健康的第一杀手,因此控制As的进程及其并发症的发生成为临床治疗心脑血管疾病的首要目标。近年的研究发现,As斑块内常出现病理性新生血管,它们能促进As的发展,甚至导致斑块破裂及其并发症的发生,因此抑制斑块内血管新生,能增强斑块的稳定性,甚至可能使斑块消退,达到减少临床心脑血管疾病发生的目的。
中医学认为,As的病因病机为饮食失宜、劳倦内伤、年老体虚复感外邪,导致气滞、痰浊、血瘀互结阻滞经脉而引发的本虚标实之证。As斑块内的病理性新生血管形成目前在中医学认为属于络病范畴,与络道增生无度,亢变为害有关。中医药防治As具有安全、疗效稳定并可长期应用的优势,许多中医药对As斑块内血管新生的干预研究均表明,中医药能有效抑制As斑块内新生血管的形成,从而延缓As的进程,逆转斑块增生甚至消减斑块,达到防治As的目的。
我的导师罗陆一教授认为肾气亏虚、痰瘀阻络是导致As及其斑块形成的重要病机,认为络道增变是As斑块内血管新生的根本病机。他根据多年临床研究结合现代科研资料,研制成兼有补肾、活血、化痰等作用的复方中药制剂通脉地仙丸,经过多年科研和临床证明,通脉地仙丸具有显著的抗氧化、扩血管、改善循环等作用,作为我院的院内制剂广泛用于临床治疗冠心病、脑梗塞等As疾病,取得满意疗效。
为了进一步研究通脉地仙丸在防治As发生发展中的作用机制,本课题从As斑块内新生血管出发,通过文献总结中西医学对As斑块内新生血管的研究进展,并通过临床试验和动物实验研究,观察与As斑块以及新生血管有关的指标,从而探讨通脉地仙丸改善As疾病进程甚至消减斑块的作用机制。
1临床研究：通脉地仙丸治疗颈动脉粥样硬化(carotid atherosclerosis, CAS)的临床研究
1.1目的：研究通脉地仙丸对CAS病人总体中医证候的治疗作用,研究其改善CAS斑块和稳定斑块的作用机制,研究通脉地仙丸对CAS病人VEGF、FGF-2水平的影响。
1.2方法：观察通脉地仙丸组(以后简称中药组)和阿托伐他汀钙组(以后简称对照组)共98例CAS病人,中药组以通脉地仙丸口服,对照组服用阿托伐他汀钙,两组均用药6个月。观察病人治疗前后的颈动脉超声指标、斑块积分、血脂、中医证候积分、中医症状总疗效以及VEGF、FGF-2等指标的变化情况。
1.3结果：与治疗前相比,两组在各指标方面均有明显改善；治疗后比较,通脉地仙丸在中医症状总疗效、中医证候方面、病情程度、CAS斑块的软斑消退及减少方面、降低颈内动脉(internal carotid artery, ICA)和颈总动脉分叉处(bifurcation, BIF)的阻力指数、改善颈外动脉(external carotid artery, ECA)的搏动指数及改善血清VEGF水平方面的作用均优于阿托伐他汀钙,而在其他方面二者的治疗作用无明显差异。
1.4结论：对于CAS的病人,应用通脉地仙丸治疗,可以使软斑消退或减少,改善颈动脉彩超指标变化,更能改善病人的症候,稳定斑块,改善大脑血流供应,从而起到延缓As进程的作用。
2实验研究：通脉地仙丸对兔主动脉粥样硬化斑块内血管新生的影响及机制研究
2.1目的：探讨通脉地仙丸对As及其斑块内新生血管的作用机制,探讨通脉地仙丸稳定As斑块甚至消退斑块的机制。
2.2方法：40只雄兔随机分为4组：正常组(normal group,以下简称NG)、模型组(model group,以下简称MG)、中药治疗组(herbal treatment group,以下简称HTG)、他汀治疗组(statins treatment group,以下简称STG),每组10只。在实验开始时除NG外用高脂饲料喂养和耳缘静脉注射牛血清白蛋白制造As模型,10周后,随机观察As形成情况,以出现主动脉斑块作为成功标志。之后MG、HTG、STG均改用普通饲料喂养,NG只饲养不给药,HTG、STG在10周后开始给药,所有用药均到实验结束24周。MG给等量的生理盐水。实验前后分别抽血测TC、TG、HDLC、LDLC水平,实验结束后观察斑块内部结构以及新生血管标记物CD34、血管新生的重要因子VEGF、FGF-2的阳性染色情况,观察并计算CD34、VEGF的阳性染色面积率和FGF-2的平均光密度值,观察As斑块HE染色结构及免疫组化染色阳性表达情况,观察电镜下斑块内部细胞结构变化情况。
2.3结果：MG的血脂各项TC、TG、LDLC水平均明显高于NG,通脉地仙丸和阿托伐他汀钙均能有效改善As的TC、LDLC水平,阿托伐他汀钙改善As的TC水平的效果优于通脉地仙丸,通脉地仙丸改善As的LDLC水平的效果优于阿托伐他汀钙,通脉地仙丸对As的HDL-C水平有治疗作用；无论是大体标本观察还是HE染色、免疫组化染色以及电镜下观察,HTG和STG改善As斑块的作用均表达明显,两种治疗方法均能有效改善As斑块内CD34阳性染色面积表达,从而有效改善斑块内新生血管面积,另外通脉地仙丸能有效改善斑块内VEGF的阳性染色面积的表达,二者均未能影响FGF-2在As斑块中的阳性表达的变化。
2.4结论：说明本次实验As动物模型制造成功,血脂水平显著升高；通脉地仙丸和阿托伐他汀钙均能有效改善As的血脂情况,二者均能有效改善斑块内新生血管面积。在改善斑块内新生血管面积、减小或者消退斑块方面,通脉地仙丸的作用明显优于阿托伐他汀钙；说明通脉地仙丸能显著稳定或消退As斑块,从而延缓As疾病进程。
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 rabbits
2.1 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.
中医学认为,As的病因病机为饮食失宜、劳倦内伤、年老体虚复感外邪,导致气滞、痰浊、血瘀互结阻滞经脉而引发的本虚标实之证。As斑块内的病理性新生血管形成目前在中医学认为属于络病范畴,与络道增生无度,亢变为害有关。中医药防治As具有安全、疗效稳定并可长期应用的优势,许多中医药对As斑块内血管新生的干预研究均表明,中医药能有效抑制As斑块内新生血管的形成,从而延缓As的进程,逆转斑块增生甚至消减斑块,达到防治As的目的。
我的导师罗陆一教授认为肾气亏虚、痰瘀阻络是导致As及其斑块形成的重要病机,认为络道增变是As斑块内血管新生的根本病机。他根据多年临床研究结合现代科研资料,研制成兼有补肾、活血、化痰等作用的复方中药制剂通脉地仙丸,经过多年科研和临床证明,通脉地仙丸具有显著的抗氧化、扩血管、改善循环等作用,作为我院的院内制剂广泛用于临床治疗冠心病、脑梗塞等As疾病,取得满意疗效。
为了进一步研究通脉地仙丸在防治As发生发展中的作用机制,本课题从As斑块内新生血管出发,通过文献总结中西医学对As斑块内新生血管的研究进展,并通过临床试验和动物实验研究,观察与As斑块以及新生血管有关的指标,从而探讨通脉地仙丸改善As疾病进程甚至消减斑块的作用机制。
1临床研究：通脉地仙丸治疗颈动脉粥样硬化(carotid atherosclerosis, CAS)的临床研究
1.1目的：研究通脉地仙丸对CAS病人总体中医证候的治疗作用,研究其改善CAS斑块和稳定斑块的作用机制,研究通脉地仙丸对CAS病人VEGF、FGF-2水平的影响。
1.2方法：观察通脉地仙丸组(以后简称中药组)和阿托伐他汀钙组(以后简称对照组)共98例CAS病人,中药组以通脉地仙丸口服,对照组服用阿托伐他汀钙,两组均用药6个月。观察病人治疗前后的颈动脉超声指标、斑块积分、血脂、中医证候积分、中医症状总疗效以及VEGF、FGF-2等指标的变化情况。
1.3结果：与治疗前相比,两组在各指标方面均有明显改善；治疗后比较,通脉地仙丸在中医症状总疗效、中医证候方面、病情程度、CAS斑块的软斑消退及减少方面、降低颈内动脉(internal carotid artery, ICA)和颈总动脉分叉处(bifurcation, BIF)的阻力指数、改善颈外动脉(external carotid artery, ECA)的搏动指数及改善血清VEGF水平方面的作用均优于阿托伐他汀钙,而在其他方面二者的治疗作用无明显差异。
1.4结论：对于CAS的病人,应用通脉地仙丸治疗,可以使软斑消退或减少,改善颈动脉彩超指标变化,更能改善病人的症候,稳定斑块,改善大脑血流供应,从而起到延缓As进程的作用。
2实验研究：通脉地仙丸对兔主动脉粥样硬化斑块内血管新生的影响及机制研究
2.1目的：探讨通脉地仙丸对As及其斑块内新生血管的作用机制,探讨通脉地仙丸稳定As斑块甚至消退斑块的机制。
2.2方法：40只雄兔随机分为4组：正常组(normal group,以下简称NG)、模型组(model group,以下简称MG)、中药治疗组(herbal treatment group,以下简称HTG)、他汀治疗组(statins treatment group,以下简称STG),每组10只。在实验开始时除NG外用高脂饲料喂养和耳缘静脉注射牛血清白蛋白制造As模型,10周后,随机观察As形成情况,以出现主动脉斑块作为成功标志。之后MG、HTG、STG均改用普通饲料喂养,NG只饲养不给药,HTG、STG在10周后开始给药,所有用药均到实验结束24周。MG给等量的生理盐水。实验前后分别抽血测TC、TG、HDLC、LDLC水平,实验结束后观察斑块内部结构以及新生血管标记物CD34、血管新生的重要因子VEGF、FGF-2的阳性染色情况,观察并计算CD34、VEGF的阳性染色面积率和FGF-2的平均光密度值,观察As斑块HE染色结构及免疫组化染色阳性表达情况,观察电镜下斑块内部细胞结构变化情况。
2.3结果：MG的血脂各项TC、TG、LDLC水平均明显高于NG,通脉地仙丸和阿托伐他汀钙均能有效改善As的TC、LDLC水平,阿托伐他汀钙改善As的TC水平的效果优于通脉地仙丸,通脉地仙丸改善As的LDLC水平的效果优于阿托伐他汀钙,通脉地仙丸对As的HDL-C水平有治疗作用；无论是大体标本观察还是HE染色、免疫组化染色以及电镜下观察,HTG和STG改善As斑块的作用均表达明显,两种治疗方法均能有效改善As斑块内CD34阳性染色面积表达,从而有效改善斑块内新生血管面积,另外通脉地仙丸能有效改善斑块内VEGF的阳性染色面积的表达,二者均未能影响FGF-2在As斑块中的阳性表达的变化。
2.4结论：说明本次实验As动物模型制造成功,血脂水平显著升高；通脉地仙丸和阿托伐他汀钙均能有效改善As的血脂情况,二者均能有效改善斑块内新生血管面积。在改善斑块内新生血管面积、减小或者消退斑块方面,通脉地仙丸的作用明显优于阿托伐他汀钙；说明通脉地仙丸能显著稳定或消退As斑块,从而延缓As疾病进程。
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 rabbits
2.1 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.
引文
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