| The concept of sleep deprivation (SD) originated in the continuing/continuous working state lead to lack of sleep. It describes a process and status that person loss of the required amount of sleep because of the environment or himsely reasons. Generally, sleep less than6-8hours within24hours, means it take place SD. With the accelerated pace of modern life and social competition, SD become a very important social issue. SD in some occupations or groups is inevitable. We often heard of some reports of heart attack or sudden death at worse due to continuing working and insufficient sleep.SD can influence the body inherent biological rhythm, so that the body was in stress state. Stress is the body reaction for various kinds of harmful stimulation. The body will occur rapid mobilization of defensive protection and at its best state in early period of stress. However, t he duration is short. Then the body state is going into the resistance or adaptation stage. Noxious stimulation is continuing strongly deplete to the body’s resistance. At that time, the internal environment is significantly imbalanced. The negative effects of stress including stress-related diseases, organ function decline, even shock and death have become more obviously.When body was strongly stimulated, the changes of the neuroendocrine response to stress were the strongly excited of locus coeruleus-norepinephrine neurons/sympathetic-adrenal axis and hypothalamus-pituitary-adrenal (HP A) axis. The role of HPA axis involved in stress response is the most important. When HPA axis was activated, it can accelerate the release of corticotropin releasing hormone, thereby, stimulating the secretion of adrenocorticotropic hormone (ACTH), increased cortisol (CORT) secretion,. Activity of HPA axis can be changed affected by various stress stimuli in vivo and vitro. The levels of ACTH directly reflect the state of HPA axis function. CORT is the end products of HPA axis. It has important implication for glucose, fat and protein metabolism of body. Therefore, it is considered as one of the most classic and important indicators in stress research. CORT can directly affect glucose, protein and fat metabolism, suppress immune function, increased the reactivity of cardiovascular system on catecholamine and other pressurized reactive substances. It also can strengthen of norepinephrine on contraction of the artery, accelerate the liver produce angiotensinogen. It can combine with renin into renin-angiotensin. It caused Na+, H2O retention, increased blood volume, elevated blood pressure. It can induce leukocytosis, increase the production of oxygen free radicals. The oxygen free radical can damage to structure and function of vascular endothelial cells. When the permeability of endothelial cells Increased, it lead lipid can easily invade intima, then the occurrence and development of AS is accelerated. Recent researches have reported that occur and development process of coronary heart disease is closely related to HPA axis.Oxidative stress means imbalance between body antioxidants and the oxide generating system. Organisms can produce reactive oxygen species when they are doing for aerobic metabolism. Under normal circumstances, the production and clear of oxygen free radicals in vivo is balanced. When too many free radicals or antioxidants in vivo relatively low, free radicals in the body will imbalance. When the accumulation of free radicals in the body is excessively, it will attack the body, that is, oxidative stress. SD can induce oxidative stress by a variety of ways. Three ways, specifically including the cause of energy metabolism and expenditure and the increase in free radicals after SD, reduced antioxidant capacity as well as through the endoplasmic reticulum stress induced oxidative stress indirectly. In oxidative stress conditions, elevated catecholamine and glucocorticoid can mobilize the body in all aspects of the mechanism to cope with the free radical generation and scavenging imbalance occur in the body. A large number of free radicals accumulation in the body, then they caused extensive damage.Atherosclerosis (AS) is a common and frequently-occurring disease, it is seriously harm to public health. In recent years, AS has an increasing trend in China. AS is a disease in large and medium arteries, such as coronary, carotid arteries, the arteries of the extremities and elastic arteries (e.g. aorta, iliac arteries), arterial lumen can be blocked by Atherosclerotic plaques. As is a disease prone to blood clots, bleeding, thrombosis and arterial rupture, it can lead to serious consequences. Currently considered that the occurrence and development of AS is related to inflammatory reaction. Recent studies have pointed out that AS is essentially a complex, slow progress of the inflammatory process. Inflammation is playing an important role in all stages of AS, including the occurrence and development of AS, plaque surface rupture and finally complicated with thrombosis. There are more reports about SD affects the release of inflammatory cytokines, indicate that SD can trigger the stress response which led to the release of various inflammatory protein. These inflammatory proteins can also endanger the cardiovascular system.In recent years, more and more evidence of acute cerebral and cardiac ischemia clinical events, indicated that AS unstable plaques is a more dangerous factor than arterial stenosis. The occurrence of acute coronary syndrome is often closely related to some unstable plaques and secondary thrombosis. These patches often do not lead to severe stenosis, it prone to rupture, erosion, calcification, etc. and easily to secondary thrombosis, lead to the clinical high risk events. Accumulation of lipid-rich macrophage foam cells in AS Injury is an important feature of plaque easy to break. Macrophages secrete matrix metalloproteinase (MMPs), witch play an important role in plaque rupture. MMPs are now thought as an independent risk factor of atherosclerosis and coronary heart disease, MMP-9is an important member of the family of MMPs. MMP-9plays an important role in vascular remodeling in AS plaque, unstable plaque and its rupture induced acute coronary syndrome.In this study, we used "modified multiple platform method of SD" to establish SD model with AS rats. After1,3,5,7days of SD respectively, we tested the changes of trends of related indicators of neuroendocrine function, oxidative stress, inflammation in serum and aortic tissue of AS rats in each group. We use the expression levels of protein of MMP-9in aortic tissue as an indicator for evaluating plaque stability. At the same time, we observed the physiological, behavioral changes, changes of electrocardiograme and morphological changes of the aorta. We explored that whether the aortic tissue of AS rats will be damaged by SD-induced changes in neuroendocrine function, oxidative stress, response of inflammatory after SD. We explored that whether SD can accelerate the development of plaque rupture leading to acute cardiovascular and cerebrovascular events.Chapter one:the influence of the changes of neuroendocrine function in atherosclerotic rats after sleep deprivationObjective:To observed the fluctuations of expression of adrenocorticotropic hormone (ACTH) and cortisol (CORT), two closely related with cardiovascular disease hormones produced by the neuroendocrine system, in the serum at different time under SD, analysis the functional status of HPA axis, and reflect changes of neuroendocrine function in SD rats.Methods: (1) Established rat model of AS.(2) Established AS rat model of SD.(3) Observed the physiological and behavioral changes in AS rats after SD.(4) Tested content of ACTH and CORT in serum in AS rats after SD.Results:(1) The mental state of AS rats was gradually deteriorated, response dull, loss of appetite, body weight loss gradually, variable weak, fur become rough, unkempt and not gloss, after SD. With the time of SD, AS rats was first excited, then irritated, at the last failure.(2) The levels of ACTH and CORT in AS rats were in the volatility of changes after SD. Witch is increased at first and then declined.Conclusions:Stress stimulation caused by SD can activate the HPA axis, stimulated the secretion of ACTH and CORT related closely with cardiovascular risk factors. With the time of SD, levels of hormones secreted were in the volatility of changes, then they feedback to the changes of stress. Thus SD can impact on the cardiovascular system, accelerate the progress of AS in AS rats.Chapter two:the influence to the levels of oxidative stress in atherosclerosis rats after Sleep deprivationObjective:Represented by glutathione (GSH), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase(SOD), four important indicator of oxidative stress, observed oxidative stress and changes in trends in aortic tissue of AS rats under SD. Understand the influence to SD-induced oxidative stress on the process of AS disease in AS rats.Methods:(1) Established rat model of AS.(2) Established AS rat model of SD. (3) Detected contents of GSH and MDA in aortic tissue of AS rats after SD.(4) Detected activity of GSH-Px and SOD in aortic tissue of AS rats after SD.(5) Analyzed the correlation between various indicators and the time of sleep deprivation.Results:(1) The content of GSH in aortic tissue of AS rats was reduced after SD. With the time of SD, it showed decreasing trend.(2) The activity of GSH-Px in aortic tissue of AS rats was reduced after SD. With the time of SD, it showed decreasing trend.(3) The activity of SOD in aortic tissue of AS rats was increased significantly and reached the highest value at the first day of SD. With the time of SD, it showed decreasing trend.(4) The content of MDA in aortic tissue of AS rats was increased after SD. With the time of SD, it showed increasing trend.(5) The time of sleep deprivation was negatively correlated with GSH、GSH-Px and SOD (r=-0.949,-0.977,-0.590, P<0.001), and was positively correlated with MDA(r=0.984, P<0.001).Conclusions:The oxidative stress occurred in AS rats after SD. With the time of SD, the body’s antioxidant capacity is gradually weakened, suffered more severe oxidative damage, thus speeding up the development process of AS lesions.Chapter three:the influence to the levels of inflammatory cytokines in atherosclerosis rats after Sleep deprivationObjective:We used serum and aortic tissue in AS rats as samples to detect the levels of tumor necrosis factor-a (TNF-a), hypersensitivity-creactive protein (hs-CRP), interleukin-6(IL-6) in serum and expression levels of protein of nuclear factor-kappa B (NF-κB) in aortic tissue, with different times of SD. Understand whether SD can cause inflammation reaction in AS rats with time of SD, and the trend of reaction extent. We explored that whether inflammatory reaction can be activated by SD, so that the process of development will be accelerated by inflammatory reaction.Methods:(1) Established rat model of AS.(2) Established AS rat model of SD.(3) Detected the levels of TNF-a, hs-CRP, IL-6in serum of AS rats after SD.(4) Detected the expression levels of protein of NF-κB in aortic tissue of AS rats after SD.(5) Analyzed the correlation between various indicators and the time of sleep deprivation.Results:(1) The levels of TNF-a in serum of AS rats was increased after SD. With the time of SD, it showed increasing trend.(2) The levels of hs-CRP in serum of AS rats was increased after SD. With the time of SD, it showed increasing trend.(3) The levels of IL-6in serum of AS rats was increased after SD. With the time of SD, it showed increasing trend.(4) The expression levels of protein of NF-κB in aortic tissue of AS rats was increased after SD. With the time of SD, it showed increasing trend.(5) The time of sleep deprivation was positively correlated with TNF-α、 hs-CRP、IL-6and NF-κB (r=0.952,0.951,0.961,0.986, P<0.001).Conclusions:Inflammatory reaction was activated in AS rats after SD. Inflammatory reaction sustainable development, and AS lesions in aortic tissue of AS rats deepened with the time of SD. SD can activate inflammatory reaction leading to accelerate the process of development of AS.Chapter four:the influence to the stability of plaque in atherosclerosis rats after Sleep deprivationObjective:In this study, we use As rats after SD as the research object, observed the electrocardiogram performance, morphological changes of the aorta by microscope, detected the expression levels of protein of MMP-9in aortic tissue as an indicator for evaluating plaque stability. Understand the changes of indicators mentioned above with the time of SD. We explored that whether SD can accelerate the development of plaque rupture leading to accelerate the process of development of AS. Analyzed related indicators of neuroendocrine function, oxidative stress and inflammation mentioned above by multiple stepwise regression method to find out indicators that can influence the expression levels of protein of MMP-9. To make sure whether SD can influence AS rats by tress aspects, neuroendocrine function, oxidative stress and inflammation, promote the development of plaque rupture leading to accelerate the process of development of AS.Methods:(1) Established rat model of AS.(2) Established AS rat model of SD.(3) Observed the electrocardiogram performance.(4) Prepared aorta sample of AS rats and observed it by microscopy after SD.(5) Detected the expression levels of protein of MMP-9in aortic tissue of AS rats after SD.(6) Analyzed the correlation between various indicators and the time of sleep deprivation. (7) Analyzed related indicators of neuroendocrine function, oxidative stress and inflammation mentioned above by multiple stepwise regression method to find out indicators that can influence the expression levels of protein of MMP-9.Results:(1) The changes of heart rates of AS rats were large after SD. The changes of heart rates of AS rats in volatility of fast at first then slow down with the time of SD.(2) With the time of SD, ST-T of electrocardiogram elevated gradually, T wave tall and upright showed SD can induce full thickness myocardial ischemia.(3) With the SD time, the severity of AS in aortic tissue of AS rats increased gradually after SD.(4) The expression levels of protein of MMP-9in aortic tissue of AS rats was increased after SD. With the time of SD, it showed increasing trend.(5) The time of sleep deprivation was positively correlated with the changes of ST-T of electrocardiogram and MMP-9(r=0.883,0.978, P<0.001).(6) The main factors that can affect the expression levels of protein of MMP-9in aortic tissue of AS rats were ACTH、MDA、hs-CRP and IL-6.Conclusions:SD can influence AS rats by tress aspects, neuroendocrine function, oxidative stress and inflammation, change the expression levels of protein of MMP-9in aortic tissue of AS rats, promote the development of plaque rupture leading to accelerate the process of development of AS. |
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