| Backgroud and Objective: Acute coronary syndrome(ACS) is a kind of acute cardiac ischemic syndrome, its clinical manifestations include unstable angina pectoris , acute myocardial infarction or sudden cardiac death. It is a severious type of coronary artery disease. It is clear that plaque rupture, platelet aggregation, and thrombogenesis are the main mechanisms of ACS, and inflammation plays a key role in plaque unstability. The increase of serum inflammatory markers such as interleukin-6, intracellular adhesion molecule-1, C-reactive protein is closely linked with coronary plaque unstability, and is thinked as predictors of cardiovascular adverse events. The basic cause of coronary artery disease is atherosclerosis, approximately 40% atherosclerosis is involved with psychological/mental stress. Stress, especially psychological stress not only can promote atherosclerosis through living habits or chronic effect, also can induce the attack of angina and myocardial infarction, and worse the prognosis of myocardial infarction. Social psychic factors(for example, depression, hostility and anxiety) can induce ACS through increasing release of inflammatory factors and activating the monocyte in plaque, coronary spasm, resulting in thrombosis. It is reported that psychological stress promotes acute inflammatory response, leading to a increasing circulating level of CRP,IL-6,sICAM-1. And the latter participates the cell infiltrating process of atherosclerosis, promotes the emergence of atherosclerosis, and has a important effect on the onset of coronary artery disease. It is not clear that whether psychological stress has an direct effect on atherosclerotic plaque. It is also not clear that whether we can use inflammatory markers to reflex the degree of stress and the risk of cardiac event in the future. Thus, elucidating this problem has an important significance in the prevention and the therapy for ACS .Based on the atherosclerotic model of rats, the present study was designed in order to interpret the following points: to observe the direct effect of chronic emotional stress of empty bottle on inflammatory marker(ICAM-1) in atherosclerotic plaque, then to explore its role and mechanism in plaque unstability; to analyze the relationship and significance of inflammatory marker IL-6,CRP,sICAM-1 in peripheral blood and ICAM-1 in plaque, then to estimate the feasibility of using inflammatory marker in peripheral blood to reflex the degree of inflammatory in plaque ; to compare the level of inflammatory marker among different stress condition and then to explore its clinical value.Materials and Metheds: 50 male Sprague-Dawley rats weighting 180-220g were randomly divided into 2 groups: the control group(n=6) and the atherosclerotic group(n=44). The former was treated by common diet and saline intraperitoneal injection, the latter by high fatty diet and a large dose of vitamin D3 intraperitoneal injection. After 8 weeks, the atherosclerotic model were made. Then the 44 atherosclerotic model rats were divided in 3 subgroups: no-stress group(n=10), physical stress group(n=12) and emotional stress group(n=12). In physical stress group and emotional stress group, 2 times/day drinking time was cut to 1 time/day, and at the same time, emotional stress group were given empty bottle, this process last for 2 weeks. At 1 hour after the last stress, the blood samples were drawed, the serum levels of IL-6 were tested by radioimmunoassay and ICAM-1 CRP by enzyme linked immunosorbent assay. The aorta and heart were extracted for pathology examination, and the express of ICAM-1 were tested by immunohistochemical examination.Results: (1) Affirmance of atherosclerosis in atherosclerotic model rats. The critera of atherosclerosis included that the continuity of endothelium was interrupted, plaque was formed in focal vessel wall outstanding to lumina; fatty bubbles, calcification, edema, smooth muscular hyperplasy and disorder , elastorrhexis and calcification was seen in media and intima, adventitia became thin. From the HE staining of the pathologic slices of aortic and coronary arter, one or more sign of atherosclerosis were identified in 18 atherosclerotic model rats, and they were given the further study. The aortic structure in control group was normal.(2) The express of ICAM-1 in aorta in atherosclerotic group was more positive than in control group(p<0.01). Inemotional stress group was notablly higher than in no-stress group and in physical stress group(2.18±0.17vsl.58±0.22,1.22±0.15, P<0.001, respectively). In physical stress group was higher than in no-stress group (58±0.22vsl.22±0.15, P=0.001).(3) The serum level of IL-6(51.80±4.60 pg/ml vs 27.60±4.19 pg/ml,8.01±1.39 pg/ml,7.83±1.37 pg/ml), sICAM-1(1.24±0.25 vs 0.85±0.09,0.62±0.17,0.57±0.11), CRP(1.00±0. 37 vs 0.90±0.29,1.01±0.22, 0.71±0.13) in emotional stress group were significantly higher than other groups(P<0.05, respectively). There was a positive relationship between the serum level of IL-6, ICAM-1,CRP and the express of ICAM-1 in aorta(r=0.75, r=0.87, P<0.01; r=0.59, P=0.01,respectively).Conclusion: 1. In rats with atherosclerosis , emotional stress induce a increasing expression of ICAM-1 in aortic atherosclerotic plaque, meanwhile, emotional stress also induce a higher serum level of IL-6, CRP, sICAM-1 .So we reckon that in animal experimentation , emotional stress have a direct effect on the transition from stability to unstability through in-plaque and out-plaque inflammation.2. In rats with atherosclerosis, the increasing serum level of ICAM-1 ,IL-6,CRP in blood and the increasing expression of ICAM-1 in aorta were seen in emotional stress group. And there is positive relationship of inflammatory markers between in blood and in plaque.. The serum level of ICAM-1,IL-6,CRP can reflex the inflammatory degree in atherosclerotic plaque.3. In rats with atherosclerosis, there is different inflammation both in blood and in plaque in differents stress setting. High stress group has higher level of inflammatory marker. It suggests that high psychological stress may be related with increasing risk of cardiovascular event in the future. |
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