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Effect Of Yiqi Huoxue Decoction On Coronary Microcirculation Disorder And Nrf2 - ARE Signaling Pathway In Rats With Myocardial Infarction

Posted on:2017-01-27Degree:DoctorType:Dissertation
Country:ChinaCandidate:X QiFull Text:PDF
GTID:1104330482484890Subject:Integrative basis
Abstract/Summary:PDF Full Text Request
After myocardial infarction, coronary microcirculation obstruction in coronary microcirculation. Coronary microcirculation is composed of 150 um microvascular diameter of microcirculation system, including myocardial tissue micro vein, the capillaries and arterioles.Coronary microcirculation of heart blood circulation network structure, also is the main coronary artery myocardial metabolic venues and vascular bed resistance and coronary microcirculation of smooth running between myocardial cells can ensure normal exchange material, nutrition, so that it can play a normal physiology function. Therefore, more attention paid to the level of myocardial microcirculation perfusion, in-depth understanding of myocardial microcirculation perfusion can provide help for treatment of myocardial ischemia. All kinds of myocardial microcirculation on the basis of coronary artery lesions in mechanical or functional block factors can cause myocardial microcirculation perfusion. Even if no significant coronary vascular stenosis, but a microcirculation dysfunction caused by lack of microcirculation perfusion, will lead to clinical adverse events, and this shows that the importance of the prognosis of patients with coronary microcirculation perfusion for evaluation. So, how to maintain a continuous supply of blood vessels, improve the level of tissue perfusion and reduce ischemic necrosis caused by as much as possible, it is very scientific significance and to explore the necessity of structure integrity and improve microvascular damage and microvascular dysfunction is particularly important. Coronary microcirculation regulation is a variety of regulatory mechanisms, including:metabolic, humoral factors, nerve and muscle source sex. This article is in prophase of "yiqi huoxue traditional Chinese medicine (TCM) on rat myocardial infarction coronary microvascular dysfunction and related molecular regulatory mechanism", on the basis of to "yiqi huoxue medicine effect on rat myocardial infarction coronary microcirculation and Nrf2-ARE signaling pathways link" about further reveals the related mechanism.This research is divided into last and next two parts, the last to review research, discusses the pathophysiology, and treatment of coronary microcirculation, Nrf2-ARE signaling pathways for cardiovascular protective effect and mechanism of the study and research progress of traditional Chinese medicine of myocardial infarction. Next to the experimental research, including five parts, the concrete research content is as follows:ObjectiveResearch on rat myocardial infarction coronary microcirculation change, relevant regulation and the mechanism of action of yiqi huoxue medicine.MethodThis subject adopts the classic model of rat myocardial infarction (AMI), using SD rats left coronary artery ligation of of acute myocardial infarction (AMI) model, on the basis of ecg evaluation all building successful random grouping randomly.Respectively is:the model group, the traditional Chinese medicine (yiqi huoxue) group, stilbene yiqi dropping pill group and without perindopril captopril group, to control as the control group, were divided into 5 groups. Choose 7 and 28 days after treatment of two time points, By observing the experimental myocardial infarction rats XinGengBing change situation and related parameters of cardiac function change, evaluate the success of myocardial infarction model and yiqi huoxue medicine effect on rat myocardial infarction myocardial pathology organization; By observing the experimental myocardial infarction in the rat heart by electron microscopy techniques to observe the ultrastructure of myocardial tissue in the edge area of infarction, to explore yiqi huoxue medicine effect on myocardial tissue pathological changes of the capillary structure, including the arteries, capillaries diameter, the thickness of the capillary endothelial cells, capillary basement membrane thickness, the capillary opening rate, half open rate and occlusion rate; By using ELISA to detect the plasma ADM, AT2 and MCP 1 expression changes, observing yiqi huoxue traditional Chinese medicine (TCM) on rat myocardial infarction myocardial vascular injury active substances ADM, AT2 and inflammatory factor to express the influence of the MCP-1; Quantitative analysis of the Real-time rt-pcr technique the expression of NGF plays and TrkAmRNA, yiqi huoxue fang on myocardial infarction ischemia rat myocardial infarction model NGF, TrkAmRNA expression changes of peripheral zone; Quantitative analysis of Real-time rt-pcr technique Nrf2mRNA, SOD1mRNA, HO-1 mrna and protein expression, discusses yiqi huoxue fang of Nrf2, SOD1, HO-1 gene and protein expression.Results:Experiment one, mainly is successfully established model of rat myocardial infarction were compared after building model group and control group of rats after preoperative ecg: electrocardiogram (ecg) before and after operation control rats did not see obvious change; Model group rats after anterior descending ligation that is visible lead electrocardiogram (ecg) II ST segment elevation and persist, compared with the preoperative dynamic change; General HE staining observation, order control of myocardial cells, did not see myocyte hypertrophy phenomenon; Model of myocardial nuclei were compared with control group increased obviously, enlargement of myocardial fibers; Five days after building successful rat ECG showed that in the I, avL, VI-V6 can lead to different degree the formation of pathologic Q wave, and Q wave number in addition to the control group no difference between groups, which proved that myocardial infarction model was successful, and has certain stability. Than in the control group, model group left interior diameter increased (LVD), left ventricular posterior wall thickness (LVPWT), no statistical difference, yiqi huoxue group, without perindopril, and captopril group stilbene yiqi LVD slightly reduce dropping pill group compared with model group, LVPWT increases slightly, no statistical significance. Model group compared with control group of ejection fraction (EF) and short axial shortening rate (FS) significantly reduced, there is a very significant difference (P< 0.01), yiqi huoxue group, without perindopril captopril group, stilbene yiqi dropping refs EF and FS increased, there are significant differences (P< 0.01 or P< 0.05).Experiment 2, by transmission electron microscope to observe the myocardial infarction rats vascular pathological morphological changes nowadays, combined with image analysis technology semi-quantitative detection capillary diameter, the thickness of the vascular endothelial cells and basement membrane thickness change, observing yiqi huoxue fang capillary injury of myocardial infarction rats. Results:overall, yiqi huoxue medicine increased rat myocardial infarction capillary diameter, thickness of capillary endothelial cells and capillary basement membrane thickness thinning, increase the rate of its open and half open rate, reduce the rate of occlusion. Its treatment effect is better than that of without perindopril captopril group and stilbene yiqi dropping refs.Experiment 3, by using ELISA to detect the plasma to observe yiqi huoxue fang to myocardial ischemia rats plasma vasoactive substances state, ADM and inflammatory factor influence of MCP 1 expression. Results:7 days old myocardial ischemia rat model group state levels increased significantly in the control group (P< 0.01), compared with model group, yiqi huoxue and without perindopril rats plasma state expression of the captopril group were decreased significantly (P< 0.01).28 days old rat myocardial ischemia model group state levels increased significantly in the control group (P< 0.01), compared with model group, the treatment group rats plasma state levels were significantly reduced (P< 0.01).7 days old rat myocardial ischemia model group ADM levels increased significantly in the control group (P < 0.01), compared with model group, yiqi huoxue, stilbene ginseng yiqi dropping pill group and without perindopril captopril group rats plasma ADM levels were significantly fewer (P< 0.01).28 days old rat myocardial ischemia model group ADM levels did not change significantly compared with control group, compared with model group, the content of each treatment group rats plasma ADM wei qi and beneficial group were significantly increased (P < 0.01).7 days old rat myocardial ischemia and the level of the MCP-1 model group was obviously higher than that of control group (P< 0.01), compared with model group, yiqi huoxue traditional Chinese medicine dropping pill and stilbene yiqi group and without perindopril captopril group rats plasma MCP-1 levels were significantly lower (P< 0.01). Yiqi huoxue Chinese medicine group is more apparent.28 days old rat myocardial ischemia model, the expression of MCP-1 were compared with control group increased significantly (P< 0.01), compared with model group, the treatment group rats plasma MCP-1 levels were significantly lower (P< 0.01).28 days old rat myocardial ischemia model group TrKA mRNA expression significantly increased in the control group (P< 0.01), compared with model group, the treatment group yiqi huoxue medicine dropping pill and stilbene and yiqi group rats TrKA mRNA expression were significantly decreased, significant statistical significance (P< 0.01), and compared with the group without perindopril Plymouth has statistical significance (P< 0.05). Myocardial ischemia model group 7 days of rat myocardial infarction model NGF mRNA expression level increased significantly in the control group (P< 0.01), the treatment group compared with model group, the expression of myocardial infarction rats NGFmRNA were reduced (P< 0.05).28 heavenly heart infarction myocardial ischemia rat model group model NGF mRNA expression significantly increased in the control group (P< 0.01), compared with model group, yiqi huoxue medicine dropping pill dropping pill and stilbene yiqi group rat myocardial infarction model NGF mRNA expression were significantly decreased, there was a significant statistical significance (P< 0.01), and compared with the group without perindopril Plymouth has statistical significance (P< 0.05). Experiment of five: the Real-time rt-pcr technique quantitative analysis, discusses yiqi huoxue fang of Nrf2, SOD1, HO-1 gene and protein expression. Results:myocardial ischemia rat myocardial infarction model group 7 days Nrf2 mRNA expression level increased significantly in the control group (P< 0.01), the treatment group compared with model group, myocardial infarction rats Nrf2 mRNA expression increased significantly (P< 0.01).28 heavenly heart infarction myocardial ischemia rat model group Nrf2 mRNA expression significantly increased in the control group (P< 0.01), compared with model group, myocardial infarction rats Nrf2 mRNA expression increased significantly, there was a significant statistical significance(P< 0.01). Myocardial ischemia rat myocardial infarction model group 7 days HO-1 mRNA expression level increased significantly in the control group(P< 0.01), the treatment group compared with model group, the rat myocardial infarction HO-1 mRNA expression significantly increased (P< 0.01).28 heavenly heart infarction myocardial ischemia rat model group HO-1 mRNA expression significantly increased in the control group (P< 0.01), compared with model group, mi HO-1 mRNA expression in rats increased significantly, there was a significant statistical significance (P< 0.01). Myocardial ischemia rat myocardial infarction model group 7 days SOD-1 mRNA expression level significantly decreased in the control group (P< 0.01), the treatment group compared with model group, SOD of rats myocardial infarction 1 mRNA expression increased significantly(P< 0.01). SOD 28 heavenly heart infarction myocardial ischemia rat model group 1 mRNA expression of a significant decrease in the control group (P< 0.01), compared with model group, SOD of rats myocardial infarction 1 mRNA expression increased significantly, there was a significant statistical significance (P< 0.01).Conclusion:1. The increase of yiqi huoxue medicine by capillary diameter, reduce capillary endothelial cells and basement membrane thickness, increase the capillary opening rate and the rate of half open, reduce capillary occlusion rate and increase vascular substance, decrease the blood vessels, reducing the release of inflammatory substances, reduce ventricular remodeling and peripheral nerve reconstruction, improve coronary microcirculation, thus reduce the myocardial ischemia.2. Coronary microcirculation and Nrf2-ARE associated signaling pathways regulating Nrf2-ARE signaling pathways of Nrf2 mRNA, SOD 1 mRNA, HO-1 mRNA expression level increased significantly. Yiqi huoxue medicine through regulating Nrf2-ARE signaling pathways, play the role of improving myocardial ischemia.
Keywords/Search Tags:Myocardial infarction, Nrf2 signaling pathway, Vascular, Yiqihuoxue parties
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