| BackgroundCoronary heart disease(CHD)is the main cause of human health hazards.The disease mainly occurs in the elderly population.Current coronary intervention is mature.Coronary angiography(CAG)has been widely used in clinical,followed by the detection of CHD is also increasing.Slow coronary flow(SCF)phenomenon is one of them.SCF refers to the coronary artery which is not obvious stenosis lesions have occurred contrast perfusion delay.The incidence of SCF at home and abroad reported different.There have been reports of about 7% of the presence of SCF among chest pain in patients with CAG.Owing to pathophysiological characteristics and complications of the elderly patients with CHD,it is extremely complex and a serious threat to the safety of them.And it brings about great difficulties of the clinical treatment.At present,the diagnosis of SCF only rely on CAG.CAG is invasive and has a certain risk.So to find simple diagnosis or prediction method of SCF become one of the hot spots of current SCF research.Previous studies have shown that vascular endothelial function and oxidative stress played an important role in the occurrence,development and evolution of SCF.SCF may be a disease of vascular endothelial dysfunction.However,the explicit pathophysiological mechanism of SCF is still unclear.Lack of effective intervention strategies and a good evaluation of human vascular endothelial dysfunction indicators and means.In addition,the study population is limitated and the sample size is small.Especially for the elderly SCF research is rare.The current study does not fully reflect the clinical risk factors of SCF in older age(age≥65 years)and its relationship with vascular endothelial dysfunction.Therefore,the urgent need for coronary artery endothelial dysfunction in the basic and clinical aspects of in-depth study is necessary.The elderly population is an independent research group.Aiming to make a comprehensive evaluation of the current elderly SCF and vascular endothelial dysfunction.By analyzing the elderly vascular endothelial dysfunction related risk factors,not only can find out the relevant risk factors,but also find a better correlation evaluation indicators and methods.It brings a new perspective to the prevention and treatment of CHD.And it is important for the prevention and treatmentof cardiovascular disease.Cinnamaldehyde(CA)is the main active ingredient of cinnamon.Recent pharmacological studies have shown that it has significant cardiovascular protection.Including the protection of cardiomyocytes,the role of relaxation of blood vessels and so on.But its role in aging-related vascular endothelial dysfunction and related mechanisms is unclear.Studies have confirmed that it can significantly increase the important endogenous anti-oxidative stress targets-nuclear factor E2-related factor(Nrf2).It has the role of protection of liver,heart ischemia and reperfusion injury.Therefore,we will also establish a natural aging rat and aging endothelial cell model in this study.To observe the effect of cinnamaldehyde on aging-related vascular endothelial dysfunction and explore its mechanism.This study is divided into two parts: clinical research and basic research.Part I Analysis of risk factors of elderly patients with SCFObjectiveTo explore the risk factors of elderly patients with SCF and its relationship with vascular endothelial function.Materials and MethodsThe 195 elderly patients were divided into two groups based on the corrected TIMI frame count(cTFC):slow reflow group(n=96)and normal coronary flow(NCF)group(n=99).Clinical and laboratory data were obtained from medical records at admission.The indexes of vascular endothelial function and oxidative stress in the two groups were tested and compared.ResultsCompared to control group,SCF group were more men,more smokers and overweight/obese(P <0.01,respectively).Low red blood cell distribution width(RDW)and patelalet distribution width(PDW)(P <0.01,respectively).High level of uric acid,triglycerides,Cystatin C and GGT(P <0.01 or P <0.05,respectively).Levels of MDA,ET-1,vWF and PWV in SCF group were higher than those in the control group.While the level of SOD,GSH-Px,NO and ABI were lower than those in the control group(P<0.05,respectively).The results of correlation analysis showed the correlation of uric acid,GGT,GSH-Px,ABI,PWV level and NO level were negative(P <0.05,respectively).Vascular endothelial function and oxidative stress-related indexes and elderly SCF has a good correlation(P <0.05,respectively).In a multivariate analyses,the independently risk developing SCF increased by gender,uric acid,Apo-A1 and GGT.ConclusionGender,uric acid,Apo-A1 and GGT are independently risk associated with elderly SCF.And They may play a role in the pathophysiology of elderly SCF.Vascular endothelial function and oxidative stress are closely related to the pathogenesis of elderly SCF.Part Ⅱ Analysis on the risk factors of elderly SCF with CHD after PCI and the influence of prognosis ObjectiveTo explore the risk factors of elderly patients with SCF after percutaneous coronary intervention(PCI)and the influence of prognosis.And to analysis its relationship with vascular endothelial function.Materials and MethodsThe 175 elderly patients who were underdone PCI were divided into two groups based on the corrected TIMI frame count(cTFC):slow reflow group(n= 42)and normal coronary flow(NCF)group(n=133).Clinical and laboratory data were obtained from medical records at admission.The indexes of vascular endothelial function and oxidative stress in the two groups were tested and compared.ResultsThe overweight/obese ratio,percentage of acute myocardial infarction,emergency PCI ratio,onset-balloon time and Gensini score in SCF group were higher than those in the control group(P <0.01,respectively).Compared to control group,level of hematocrit,uric acid,GGT and Cystatin C in SCF group were higher(P <0.01,respectively).Levels of MDA,ET-1,vWF and PWV in SCF group were higher thanthose in the control group.While the level of SOD,GSH-Px,NO and ABI were lower than those in the control group(P <0.05,respectively).The results of correlation analysis showed the correlation of hematocrit,GGT,ABI,PWV level and NO level were negative(P <0.05,respectively).Vascular endothelial function and oxidative stress-related indexes and elderly SCF has a good correlation(P <0.05,respectively).In a multivariate analyses,the independently risk developing SCF increased by hematocrit,GGT,emergency PCI,onset-balloon time and Gensini score.ConclusionHematocrit,GGT,emergency PCI,onset-balloon time and Gensini score are independently risk associated with elderly SCF after PCI.And They may play a role in the pathophysiology of elderly SCF after PCI.Vascular endothelial function and oxidative stress are closely related to the pathogenesis of elderly SCF after PCI.Part Ⅲ Effect of Cinnamaldehyde on Elderly Vascular Endothelial Dysfunction ObjectiveTo explore the effect and the mechanism of Cinnamaldehyde(CA)on aging rats endothelium dependent relaxation function.Materials and MethodsNatural aging Sprague Dawley(SD)rat model and aging human umbilical vein endothelial cells(HUVECs)were constructed and used in this study.DHE stainning and DAF-2DA staining were used to detect Reactive oxygen species(ROS)and Nitric oxide(NO)levels respectively.Endothelium dependent relaxation(EDR)induced by Acetylcholine(ACh)and endothelium independent relaxation(IDR)induced by Nitroglycerin(NTG)were observed by Wire myograph.Expression of Nuclear factor E2-related factor 2(Nrf2)and the phosphorylation of eNOS were detected by western blotting.ResultsTreatment with CA decreased ROS level and promoted eNOS phosphorylation,thus increased NO level,improved EDR of carotid arteries in aging rat.CA did notaffect the IDR of carotid arteries in aging rats.Pretreatment with Nrf2 inhibitor,brusatol reversed the effects of CA.ConclusionCA attenuated the ROS level,increased the NO level hence improved the EDR is depended Nrf2 activation. |
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