Intervention Research Of Therapy Of Tonifying The Kidney And Activating Blood And Dissipating Phlegm On Inflammatory Factors Of Atherosclerotic Plaques

BackgroudIt was for more than 100 years history that the human known artherosclerosis(AS) was a kind of disease,and studied its pathogenesis.With the development of society and the improvement of people's living standard,at present,infectious disease caused the deaths is decreasing.While the atherosclerotic vascular disease(ASD) has become the world's first cause of death,including coronary heart diseases(CHD),cerebro vascular disease and periphera larterial disease.AS is a kind of disease,involved many factors of genes,environment and metabolism.In fact,in the past ten years,inflammation played a role in the AS disease progression has been clearly.A lot of research evidences indicate that inflammation plays an important role in AS' occurrence,development and evolution process.In recent years,lots of basic and clinical findings also suggest that it may be the core of AS' occurrence and development that the CHD patients in their body have the pro-inflammatory and anti-inflammatory imbalance.Artherosclerosis is a name of disease in western medicine.The motherland medicine related records can be visible at Phlegm-turbid,Vertigo,Chest Stuffiness,Stroke and Angina Pectoris in the records.With the deepening of the research,we gradually realize that AS' pathogenesis is essential the deficiency i origin and excess in superficiality,and deficiency complicated with excessiveness.It is the fundamental cause that the deficiency of heart,spleen,liver and kidney,and with phlegm and blood stasis for each of the disease resistance.The disease is in the blood and root of the viscera,and it is continuous developing because of the body deficiency and pathogenic excess.In recent years,alarge number of clinical trials showed that stagnant blood stasis theory was gradually attracted many scholars'attentions.Now for the modern medical treatment of AS is mainly by statin drugs.But with statin drugs reported clinical effects of increasing,the traditional chinese medicine(TCM) in the treatment of AS make a series of achievements,because of its overall concept and uniquecharacteristics of the syndrome differentiation and treatment.Based on the above background,this subject is based on TCM pathogenesis proposed by Professor Luo Lu-yi,which is kidney deficiency combined with phlegmand blood stasis.Also this study is with therapy of tonifying the kidney and activating blood and dissipating phlegm for therapeutic principles,with decoction of tonifying the kidney and activating blood and dissipating phlegm as the foundation formulas,with the hot research direction "inflammatory mechanisms" of AS as the main jumping-off place.The research selects the five kinds of typical inflammatory factors for clinical research and animal experiment's intervention goals,and the study focused on observation of the therapy of TCM and the statin drugs for the treatment of AS diseases has the same or similareffect or not,from various aspects of blood-lipid,inflammatory factor levels,immunohistochemistry and transmission electron microscopy.And it also discusses the TCM's influence on atherosclerotic plaque inflammatory factors,to further clarify the anti-inflammatory and stability of atherosclerotic plaque.Thus it is proved that the TCM therapy of atherosclerosis is safe and effective,and it has a better clinical effect by combination of TCM with western medicine.It has a positive meaning that to improve this integration in atherosclerosis in the diagnosis,treatment and prognosis assessment advantage.This subject mainly includes two parts,which are clinical research and animal experimental study.1 Clinical ResearchObjective:This Research observes the various influences on CHD patients bytherapy of tonifying the kidney and activating blood and dissipating phlegm,including clinical condition scores and clinical curative effect before and aftertreatment,lipid and lipoprotein and inflammatory factor levels,and the results of carotid doppler ultrasound examination through intima-media thickness(IMT),carotid plaques in types and quantities.The objective is to explore theintervention of this TCM therapeutic method on atherosclerotic plaque,inflammatory factors,and the distinct advantages of combination of TCM with western medicine in the treatment of AS.Methods:This research choosed 120 cases of CHD patients,including 68 cases of male and 52 cases of female.All patients were randomly divided into 3 groups,Traditional Chinese Medicine Group(TCMG),West Medicine Group(WMG) and Zhong Xi Group(ZXG),and there were 40 cases in each group. All three groups of patients were given orallydrug therapy for 24 weeks,which were respectively given by decoction of tonifying the kidney and activating blood and dissipating phlegm,Atorvastatin calcium and combination of TCM with western medicine. At 24 weekend,for three groups were observed on clinical condition scores and clinical curative effect before and after treatment.Also the blood lipid and serum inflammatory factor levels were detected by Automatic biochemistry analyzer and Enzyme-Linked Immunosorbnent Assay(ELISA).The IMT,carotid plaques in types and quantities were examined by carotid doppler ultrasound.These above results were compared between before and after the treatment within the groupsand between each treatment groups.The numerical values were expressed by mean±tandard deviation(X±S) and statistical analyzed with the soft ware of SPSS 15.0.The quantitative data was analysised by t-test and Variance analysis.The independent sample t-test was used in comparison among groups, paired sample t-test was used in comparison before and after treatment,and Variance analysis was ued in pairwise comparison between groups.The enumeration data was analysised by Chi-square test. Chi-square test was used in rate comparison andRidit analysis was used in ranked data.Results:(1) Compared between before and after the treatment within the groups:Threegroups of angina pectoris effect scores decreased obviously(P< 0.05 or P< 0.01).The TCM symptoms scores of TCMG and ZXG both declined dramatically(P<0.01),while there was no significant improvement in WMG(P> 0.05).There were improvements in various degrees between three groups in the obvious effective rateand total effective rate of angina curative effect,electrocardiogram(ECG) curative effect and the total effective rates of TCM syndromes.The level of theserum TC,TG and LDL-C of three groups all decreased significantly and the level of HDL-C increased obviously(P<0.01 or P<0.05).The level of five inflammatory factors,such as Fg,hs-CRP,IL-18,MCP-1,MMP-9, declined significantly(P< 0.01 or P< 0.05).The carotid artery intima-media thickness decreased obviously(P<0.05),and the carotid plaques in quantities decreased significantly(P<0.01).(2) Compared between each treatment groups:The improvement of angina pectorieffect scores in ZXG was superior to the groups of TCMG and WMG(P<0.05),and it was in balance with TCMG in the improvement of TCM symptoms scores(P>0.05). And the ZXG was superior to the groups of TCMG and WMG in the obvious effective rate of angina curative effect,ECG curative effect and the total effective rate of TCM syndromes(P< 0.01).And it was also superior to the groups of TCMG and WMG in decreaseing the level of the serum TC,TG and LDL-C,and rising HDL-C(P< 0.01).And so,it was superior to the groups of TCMG and WMG in decreaseing the level of five inflammatory factors(P<0.01).The ZXG was superior to the groups of TCMG and WMG in lessening the carotid artery intima-media thickness(P<0.01),but it was in balance with TCMG and WMG in reducing the carotid plaques in quantities(P>0.05). Conclusions:The research shows that the treatment of the therapy of tonifying the kidney and activating blood and dissipating phlegm combined with the Atorvastatin calcium can reduce AS plaque fibrous cap degradation and stabilize AS plaque,so it can achieve better block or delay progression of vulnerable plaques for action,and for individual patients it also can reverse the AS plaque,thus effectively reduce CHD patients with acute cardio-cerebro vascular events.The above functions mainly take effect through the following several aspects,such as the apparent improvement of angina pectori effect and the TCM symptoms scores,the significant effect of the obvious effective rateand total effective rate of angina curative effect,electrocardiogram(ECG) curative effect and the total effective rates of TCM syndromes,decreaseing the level of the serum TC,TG and LDL-C,and rising HDL-C,decreaseing the level of five inflammatory factors,lessening the carotid artery intima-media thickness and the carotid plaques in quantities.We can conclude that it may be one mechanism of treatment of AS by the therapy of tonifying the kidney and activating blood and dissipating phlegm,by adjusting the body lipid and inflammatory factor levels.This study opens a new direction for the treatment of AS disease by combination of TCM with western medicine and provide a scientific,objective and strong theoretical basis.2 Animal Experimental StudyObjective:The study investigates the mechanism of the inflammatory factors of the AS plaques of experimental rabbit models by therapy of tonifying the kidney and activating blood and dissipating phlegm,and to discuss the advantages of combination of TCM with western medicine in the treatment of AS and stabilizing AS plaques.The above functions mainly take effect through the following several aspects,including influence on the levels of lipid and lipoprotein,such as TC,TG,HDL-C and LDL-C and the five inflammatory factors,such as Fg,hs-CRP,IL-18,MCP-1 and MMP-9.Methods:The study selected 50 healthy male purebred rabbits of New Zealand,2weeks after feeding observation adaptability,all rabbits were randomly divided into 5 groups,Blank Control Group(BCG),Model Group(MG),Traditional Chinese Medicine Group (TCMG),West Medicine Group(WMG),Zhong Xi Group(ZXG).There were 10 rabbits in every groups,and the later four groups were made into model.Besides the BCG rabbits were feed with the ordinary food,the other four groups were all established AS model through combined method,which was feeding high-lipid diet and injecting bovine serum albumin(BSA) via rabbit's ear vein to cause autoimmune endothelial injury.MG rabbits were just given high-lipid diet to bulid the modle,not given any drug treatment.MG and other three treatment groups were feed with high-lipid diet for about 12 weeks.Compared with BCG group after becoming successful model,the treatment groups of TCMG,WMG and ZXG were treated by intragastric administration for 12 weeks,which were respectively given by decoction of tonifying the kidney and activating blood and dissipating phlegm,Atorvastatin calcium and combination of TCM with western medicine.After the treatment,at 20 weekend, three treatment groups' rabbits were observed on the levels of the blood lipid and lipoprotein, and five serum inflammatory factors.The pathological morphology of AS aorta were observed,including macroscopic observation,examined by Hematoxylin-Eoin(HE) staining,immunohistochemical study(MCP-1 and MMP-9) and transmission electron microscopy.And we also calculated the positive cells express percentage of MCP-1 and MMP-9.The numerical values were expressed by mean±standard deviation(X±S) and statistical analyzed with the soft ware of SPSS 15.0.The quantitative data was analysised by t-test and Variance analysis.The independent sample t-test was used in comparison among groups, paired sample t-test was used in comparison before and after treatment,and Variance analysis was ued in pairwise comparison between groups.The enumeration data was analysised by Chi-square test. Chi-square test was used in rate comparison.Results:(1) The detected results of lipid and lipoprotein: Compared with BCG,the level of TC,TG,HDL-C and LDL-C of the other four groups increased significantly(P< 0.01).Compared with MG,the level of the serum TC,TG and LDL-C of three treatment groups all decreased significantly and the level of HDL-C increased obviously(P<0.01 or P< 0.05).Compared between each treatment groups,the group of ZXG was superior to the groups of TCMG and WMG in decreaseing the level of the serum TC,TG and LDL-C,and rising HDL-C(P<0.05或P<0.01).And compared with TCMG,the group of WMG was superior to the TCMG in decreaseing the level of the serum TC,TG and LDL-C,and rising HDL-C(P<0.05).(2) The detected results of the five inflammatory factors:Compared with BCG before the treatment,the level of Fg,hs-CRP,IL-1,MCP-1 and MMP-9 of the other four groups increased significantly(P<0.01).The level of the five inflammatory factors,such as Fg,hs-CRP,IL-18,MCP-1 and MMP-9, declined significantly compared between before and after the treatment within the three groups(P<0.01 or P< 0.05).Compared between each treatment groups,with MG,the level of the five inflammatory factors of the three treatment groups declined significantly(P<0.01).The group of ZXG was superior to the groups of TCMG and WMG indecreaseing the level of five inflammatory factors(P< 0.01).And compared with TCMG,the group of WMG was superior to the TCMG in decreasing the level of the hs-CRP(P<0.05),but the other four indicators had no differences(P>0.05).(3) The comparison of the positive cells express percentage of MCP-1 and MMP-9:Compared with BCG,the positive cells express percentage of MCP-1 and MMP-9 in the other four groups increased significantly(P< 0.01).Compared with MG,the percentage of the three treatment groups all decreased obviously(P<0.01 or P<0.05).The group of ZXG was superior to the groups of TCMG and WMG in decreaseing the positive cells express percentage of MCP-1 and MMP-9(P<0.01),but had no differences between TCMG and WMG(P> 0.05).Conclusions:(1) It is a successful method to establish rabbits AS model through feeding high-lipid diet and injecting bovine serum albumin via rabbit's ear vein.(2) The research shows that the treatment of the therapy of tonifying the kidney and activating blood and dissipating phlegm combined with the Atorvastatin calcium may be superior to the groups of TCMG and WMG in improving the level of the lipid and lipoprotein.We can conclude that it may be one mechanism of treatment of AS and stabilizing AS plaque by adjusting the body lipid levels.(3) The therapy of tonifying the kidney and activating blood and dissipating phlegm combined with the Atorvastatin calcium may be superior to the groups of TCMG and WMG in decreasing the levels of five inflammatory factors and the positive cells express percentage of MCP-1 and MMP-9.We can draw the conclusion that the combination of TCM with western medicine can achieve better block or delay progression of vulnerable plaques.The above functions mainly take effect through the following several aspects,such as restraining the levels of inflammatory factors of rabbits's AS plaque,reducing AS plaque fibrous cap degradation and stabilizing AS plaque.We can infer that the levels of inflammatory factors may be a important element to decide plaque ulnerability.(4) Kidney deficiency combined with phlegm and blood stasis is one of the most important pathogenesis,which can influence the occurrence and development of AS.The combination therapy mode of tonifying the kidney and activating blood and dissipating phlegm combined with the Atorvastatin calcium can have effcet from different angles and more targets on regulating the levels of blood lipid,decreaseing the levels of inflammatory factors,restraining AS plaque fibrous cap degradation and protecting vascular endothelial cells function,and so on.Thus it can achieve better block or delay progression of vulnerable plaques for action,and effectively reduce the corresponding to the incidence of adverse events. So we infer that it can restrain the relevant inflammatory factors of AS patients through the therapy of tonifying the kidney and activating blood and dissipating phlegm.