| Reasearch background and purpose:Coronary heart disease(short for CHD)is the common disease of internal medicine and frequently occurring illnesse,which is also one of the main causes that lead to human deaths.There are about1.1million people each year die from coronary heart disease.Thrombolytic therapy, percutaneous coronary intervention(short for PCI)and cornary artery bypass graft(short for CABG) is the most effective way of narrowing the scope of acute myocardial infarction in acute myocardial infarction infarction,ami(short for AMI),and improving clinical outcomes.However, some patients and animals’function and metabolism of ischemia-induced obstacles and structural damage further increased after the myocardial ischemia-reperfusion,this phenomenon is called myocardial ischemia/reperfusion injury(short for MIRI),with the clinical manifestation of collapse in blood pressure,cardiac insufficiency,cardiac arrhythmias, even the phenomenon of broken sideng deteriorationan after the recanalization of occlusive coronary artery and the reconstruction of reconstruction area hemoperfusion.In pathological cases,there exist varying degrees of coronary microvascular remodeling, exacerbate the hdeterioration of eart function and myocardial fiber ring, what makes the clinical symptoms and prognosis of patients have no basical improvement,so that some researchers put forward that the best treatment for patients with myocardial infarction should also be working to reduce microvascular damage, to improve blood flow in infarcted myocardium perfusion.Endothelial cells distribute on heart and the vascular wall within layer, has the fuction of vascular barrier, perception and effect, they also can synthesize and secrete multiple vascular activity material by since secretion and next secretion way, regulate vascular shrink and diastolic, blood coagulation and fiber dissolved, white cell and platelet’s adhesion,vascular smooth muscle cell proliferation and so on,wich playing a key role in the occurs and development process of CHD.Vascular relaxing factor-NO and vasoconstrictive factor EF-1play an important role in regulations. THe hypoeccrisis of NO, the increasing of ET-1will lead the persistent vasoconstriction,increase myocardial ischemia injury.Von Willbrand factor(vWF) is one of the reflecting reliable indicator of impaired endothelial cells, one risk factor of the patients with coronary heart disease,which will be a research hot spot.EPCR、TM both produced by the secretion of vascular endothelial cells,they are main components of protein Csystem.Participate in activation mediated by protein kinase c signaling system, mainly related to the coagulation, fibrinolytic and inflammatory response to maintain an important role in micro-vascular homeostasis.These factors of arrhythmia in regulating coronary microvascular function and tissue blood supply has important implications.The supplementing Qi and activating blood prescriptions are made up by astragalus membranaceus, angelica sinensis, radix ginseng,, and rhizoma chuanxiong.Early results suggest that supplementing Qi and activating blood circulation can significantly promote angiogenesis in ischemic myocardium of rat myocardial ischemia, have a significant effect on related proteins and Cytokines, dose-effect relationship, particularly for supplementing Qi and activating blood circulation drugs2:1group is the most significant one and the28th day is the best to describe the problem.This subject relies on the large rats myocardial deficiency blood classic model, under the direction of the theory of qi and blood, takes the injury of coronary endothelial as an entering point, with the technology methods of micro image analysis, immunohistochemistry and so on, to dynamically observe the micro changes of myocardial ultrastructure,and observe EPCR in plasma, the expression of TM, changes of serum, plasma VWF and NO, ET-1, clarifying the molecular regulation of vascular injury active substance so as to further reveal he supplementing Qi and activating blood prescriptions gorup improve coronary microvascular dysfunction and its regulatory molecular mechanism of action.To explore the basic theories about " heart governing blood and vessels."Methods To creat the animal models of myocardial infarction after acute myocardial ischemia by the way of ligating left anterior descending coronary artery in male SD rats.After operation model,the rats are randomly divided into3groups:model group, The supplementing Qi and activating blood prescriptions group (21gkgd), perindopril in the treatment group (4mgkgd).And with the false operation group in which one the rats are only be threaded not ligated,4groups,totally.Then, giving the rats medicines by intragastric administration, the operation group and model group given the same volume of sterile distilled water, making the ECG detection5days after the operation model.Then all be killed and obtain the materials needed on the28th day. Dyed with the HE method,and make observation of myocardium pathological changes and the content of NO in serum, plasma vWF TM, EPCR,ET-1through electron microscopy and immunohistochemical method.Result(1) Myocardial pathological morphology:In operation group,the rats’s heart muscular fibers lined in tidy, with the completment of mitochondrial Crest and membrane, nuclear week gap slightly expanded. While in model group the heart muscular fibers lined diorders,nuclear and nuclear-week are severe edema, nuclear membrane partly disappearing; severe swelling deformation of mitochondrial Ridge and film, dissolved and disappeared. Compared with the model group, in the supplementing Qi and activating blood prescriptions gorup and perindopril group myocardial injury in rats reduce significantly, myocardial fibers arranged a little disorder, the mitochondrial matrix is mild edema.(2) NO content:The content of NO in modern group is apparently low.Compare with modern group,the content of NO in surgical group, the supplementing Qi and activating blood prescriptions group and perindopril group is higher which shows Statistical significance (P<0.01or P<0.05);(3)ET-1content:The content of ET-1in modern group is apparently high.Compare with modern group,the content of ET-1in surgical group, the supplementing Qi and activating blood prescriptions group is lower is higher which shows Statistical significance (P<0.01).The content of ET-1in the supplementing Qi and activating blood prescriptions group is lower is apparently lower than the perindopril group which shows Statistical significance (P<0.01);(4) vWF content:The content of vWF in modern group is apparently high.Compare with modern group,the content of vWF in surgical group, the supplementing Qi and activating blood prescriptions group is lower is higher which shows Statistical significance (P<0.01)(5) TM content:The content of TM in modern group is apparently high.Compare with modern group,the content of TM in the supplementing Qi and activating blood prescriptions group is lower is higher which shows Statistical significance (P<0.05).The content of TM in the supplementing Qi and activating blood prescriptions group is lower than it in the surgical group;(6) EPCR content:The content of EPCR in modern group is apparently high.Compare with modern group,the content of EPCR in the supplementing Qi and activating blood prescriptions group is lower is higher which shows Statistical significance (P<0.01) Conclusions (1) Drugs for supplementing qi and activating blood circulation are able to regulate the secretion, release of vasoactive substances and the proportion of different materials by improving the function of endothelial damaged cells to have the reducing NO/ET-1normal and stable for regulating the vascular tone and regional blood volume, which recover the homeostasis of blood vessel.(2) Drugs for supplementing qi and activating blood circulation are able to reduce the expression of TM and vWF to regulate the expression of related active materials, which keep the state of anticoagulation in vascular system, for protecting endothelial damaged cells in coronary micro circulation.(3) Drugs for supplementing qi and activating blood circulation are able to improve the pathological changes of coronary vascular, severity degree of vascular disease and function of coagulation by reducing the expression of EPCR, which can significantly reduce the Morbidity and Mortality of AMI.The experimental research shows:Drugs for supplementing qi and activating blood circulation are able to improve the AMI myocardial ischemia by increasing the expression of NO and reducing the expression of ET-1、vWF、EPCR and TM. These drugs are able to improve the coronary large or small vascular lesions by regulating the vascular tone and keeping the state of anticoagulation in vascular system. The data shows that drugs for supplementing qi and activating blood circulation have great effects on regulating the microvascular dysfunction and reveals the control mechanism of related molecule on improving the coronary microcirculation. The research offers the experimental basis for clarifying the Chinese medicinal theory of heart governing blood and vessels. |
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