| Coronary microcirculation is the blood circulation between heart venules and small arteries, the myocardial microcirculation will affect microcirculation, causing myocardial ischemia. Now we pay more and more attention to the level of perfusion of myocardial microcirculation, and to understand myocardial perfusion can be helpful to the treatment of myocardial ischemia.A variety of mechanical or functional obstruction factors lead to myocardial microcirculation hypoperfusion on the basis of coronary artery diseas.Even in the absence of obvious coronary stenosis, but there is Microcirculation hypoperfusion caused by, which can lead to the occurrence of adverse clinical events. It indicated that the importance of coronary microcirculation to the evaluation of the prognosis of patients. Therefore, how to maintain the blood supply of blood vessels, improve perfusion level and minimize ischemia-induced necrosis, it is very scientific and necessary to explore. And to improve the integrity of the microvascular structure damage and microvascular dysfunction is particularly important.Objective The effect of supplementing qi and activating blood circulation herbs on coronary microvascular injury and regulation of related molecular,from this perspective we explore the mechanism of supplementing qi and activating blood circulation on CMD.based on the theory of "the heart dominating blood circulation and vessels" we tried to analyze the change of function and structure of heart, blood vessels, and active substance, to explore theoretical basis of "the heart dominating blood circulation and vessels"Methods The rat model was established by ligaturing the left anterior descending coronary artery. On the base of ECG evaluation all successfully modeled rats were randomly divided into the model group, group treated with supplementing qi and activating blood circulation herbs (Activating blood and supplementing Qi group), group treated with Perindopril (Perindopril group).group treated with with Tong xin luo Capsules (Tongxinluo group). The sham-operation group was taken as the control. There were totally5groups. Each group was administered with corresponding drugs daily after surgery, and Select the two observing points in time7th and28th days after treatment. To observe the change of experimental lesions of myocardial infarction and related indicators of cardiac function in rats to assess the success of myocardial infarction model making and the effects of supplementing qi and activating blood circulation Chinese medicinal on myocardial histopathological. To observe the changes of mRNA expression and protein of TM, EPCR of myocardial tissue intervented by supplementing qi and activating blood circulation Chinese medicinal, we learn how Yiqihuoxue drugs protect vascular endothelial function from the gene and protein levels, and how to improve coronary dysfunction. To observe the change of NF-kB expression of myocardial in infarct border zone and serum TNF-alpha level, we learn that to regulate the NF-kB expression and serum TNF-alpha level by the supplementing qi and activating blood circulation herbs we can improve coronary microvascular dysfunction. To observe the change of MCD and pericytes intervented by supplementing qi and activating blood circulation herbs, we explore the relation between them and their relation with CMD. To observe the change of serum TM、EPCR、NO、ET-1、PGI2and TXA2, it can provide the basis for ecploring the regulatory mechanism of supplementing qi and activating blood circulation herbs on active substances of vascular injury.Results The experimental study consists of five partsIn experimental study1,mainly established rats myocardial infarction model successfully. Compared with preoperative ECG,ECG of rats in sham group had no change,while ECG of rats in myocardial infarction model had significant changes:ECG lead Ⅱ and persistent ST-segment elevation. After HE staining methods, under ordinary light microscope, myocardial cells of rats in sham group lined normally, and had no largement, while myocardial cells of rats in MI model was significant larger, and their myocardial fiber thickened significantly.ECG of rats MI model after surgery5days showed that Ⅰ, aVL, V1-V6Can guide different levels of pathological Q waves, and there were no difference in the number of Q-wave in different groups after surgery. All these signs verified the success of establishing the MI model and having a certain degree of stability. Compared with the sham-operation group, the LVD increased and the LVPWT decreased in the model group,while the LVD decreased and the LVPWT increased a little in the Activating-blood and supplementing-Qi group, Perindopril group and Tongxinluo group compared with the model group,all these has no statistically significant. Compared with the sham-operation group,the EF and FS decreased significantly in the model group(P<0.01),while the EF and FS increased significantly in the Activating-blood and supplementing-Qi group, Perindopril group and Tongxinluo group compared with the model group(P<0.05or P<0.01).In experimental study2, to observe the changes of mRNA expression and protein of TM, EPCR of myocardial tissue in myocardial infarct border zone measured by real-time PCR and western blot separately. After administration,compared with the sham-operation group, the expression of EPCR and TM of myocardial tissue in the model group increased significantly(P<0.01);the serum levels of TM and EPCR decreased significantly in the Activating-blood and supplementing-Qi group, Perindopril group and Tongxinluo group compared with the model group(P<0.01),especially Perindopril group.After administration,compared with the sham-operation group, the protein of EPCR and TM of myocardial tissue in the model group decreased significantly(P<0.01); the protein of TM and EPCR increased significantly in the activating-blood and supplementing-qi group, perindopril group and tongxinluo group compared with the model group(P<0.01or<0.05).In experimental study3, to observe the change of MCD and pericytes in myocardial infarct border zone measured by CD34factor positive staining immunohisto-chemistry method and anti-alpha-SMA antibody positive immunohistochemical method separately after intervented with supplementing qi and activating blood circulation herbs. It showed, the MVD decreased significantly in the model group and the number of capillary pericytes increased compared with the sham-opevation group(P<0.01).The MVD increased significantly in the activating-blood and supplementing-qi group, perindopril group and tongxinluo group compared with the model group(P<0.01).In experimental study4, to observe the effects of supplementing qi and activating blood circulation herbs on serum TM and EPCR, it showed that the serum levels of TM and EPCR decreased significantly in the model group compared with the sham-operation group(P<0.01) and the serum levels of TM and EPCR decreased significantly in the activating-blood and supplementing-qi group, perindopril group and tongxinluo group compared with the model group(P<0.01).In experimental study5, to detect the positive expression of NF-kB in myo-cardial infarct border zone measured by immunohistochemical method,and to detect the serum level of TNF-α measured by Elisa. The results showed that on the7th day the serum level of TNF-a and the positive expression of NF-kB increased significantly in the model group compared with the sham-operation group(P<0.01); the serum level of TNF-α and the positive expression of NF-kB decreased significantly in the activating-blood and supplementing-qi group, perindopril group and tongxinluo group compared with the model group(P<0.05or P<0.01). On the28th day the serum level of TNF-α and the positive expression of NF-kB increased significantly in the model group compared with the sham-operation group(P<0.01); the serum level of TNF-α and the positive expression of NF-kB decreased significantly in the activating-blood and supplementing-qi group,perindopril group and tongxinluo group compared with the model group(P<0.05or P<0.01),especially the Perindopril group.In experimental study6, to observe the effects of supplementing qi and activating blood circulation herbs on serum NO,ET-1,PGI2and TXA2, it showed that the serum levels of ET-1and TXA2increased,while the serum levels of NO and PGI2decreased significantly in the model group compared with the sham-operation group (P<0.01).The serum levels of ET-1and TXA2decreased,while the serum levels of NO and PGI2increased significantly in the Activating-blood and supplementing-Qi group,Perindopril group and Tongxinluo group compared with the model group(P<0.05or P<0.01).Conclusion To administrate the supplementing qi and activating blood circulation herbs can improve coronary microvascular dysfunction in myocardial infarction rat effectively, and reduce the count of capillary pericytes, maintain the relative integrity of blood vessels, improve the blood flow of local microcirculation, reduce infarct size and increase the MCD to promote angiogenesis, so as to improve the role of regional myocardial blood supply. It can protect the function of vascular endothelial at gene protein levels, and adjust the balance between the endogenous vasoconstrictor substance and vasodilator substance, improve vascular spasm, increase myocardial blood supply, and repair the function of impaired endothelial cell, reverse the changes of cell morphology,function, metabolize caused by ischemia and hypoxia, increase regional myocardial tissue perfusion and blood supply to myocardial cells,and regulate microcirculation perfusion, in order to improve myocardial coronary microvascular dysfunction effectively.In addition, supplementing qi and activating blood circulation herbs can inhibit the expression of NF-kB and reduce serum level of TNF-alpha, to prevent the microcirculation damage caused by immunity and inflammation, prevent damage myocardial cells, in order to increase myocardial blood supply.To analyze the change of function and structure of heart, blood vessels, and active substance we explored the scientific connotation of "the heart dominating blood circulation and vessels" preliminarily,"blood vessels" are dominated by the "heart",and related with blood. The "blood" running normally is the results of regulation by neurohormonal immune system.Innovation In this paper, through the theory of collateral disease we explored the theory and clinical of CMD research from the perspective of "the heart dominating blood circulation and vessels"’, it’s an innovative clinical research. Using immunohistochemical methods, RT-PCR and Western blot technique we explore the regulatory mechanism of CMD with supplementing qi and activating blood circulation herbs from the relation with "the heart dominating blood circulation and vessels", it’s an experimental study with the novelty. |
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