| BackgroundNowadays, China has become an aging society, with the worsening of the situation, how slow the aging process has become a hot spot for researchers. Academy of Social Sciences of china has published the China Aging Development Report (2013) in2013. The report noted that China will usher in the first peak of elderly population growth, in2013the number of elderly population exceeded200million, reaching202million, aging level reached14.8%. Advanced age population will continue to grow, rising from22million in2012to23million in2013, an average annual increase of100million trend will continue until2025. With the acceleration of the growth of aging population, the number of suffering adverse cardiovascular events will increase dramatically, especially atherosclerosis, stroke, myocardial infarction and heart failure.Aging also known as senescence, usually refers to the situation in normal biological maturation, increased with age, the capability of homeostatic and decreased stress decline. It’s an irreversible phenomenon that structure, composition progressively degenerative tend death. Vascular aging is an important part of the human body in the aging. Characteristic morphological and molecular alterations such as vessel wall thickening and reduction of nitric oxide occur in the aging vasculature leading to the gradual loss of vascular homeostasis. Consequently, the risk of developing acute and chronic cardiovascular diseases increases with age.Aging has always been one of the most hot topic in the field of life sciences research. with the rapid development of molecular biology, mechanisms of aging research has developed from the cellular level, subcellular level to molecular and genetic level step by step. Now there are tens of theories associated to mechanism for aging, such as somatic mutation theory, free radical theory, The crosslinked biomolecule natural theory, theory of the immune, telomere shortening theory, genetic programming theory, mitochondrial damage theory and so on. Generally they can be summarized as the following two types. Environment injury theory of aging, representative by injury of reactive oxygen species (ROS), glycosylation, etc. And genetic factor programming theory of aging, representative by telomere shortening, ell cycle regulatory factors, aging gene, etc.Since Denham Harman proposed the free radical theory of aging mechanism. It’s widely recognized that Oxidative stress is closely related to the aging process and age-related diseases.The theory noted that aging is caused by free radical damage. Reactive oxygen species (ROS) is an important factor of aging. Free oxygen radicals or reaetive oxygen species(ROS)includ ehydroxyl radicals(OH-),superoxide anion radieal(02-),hydrogen peroxide(H2O2). The cells will produce free radicals in the biological metabolic processes. It’s a normal metabolic intermediates. Meanwhile, the body exists in the corresponding antioxidant defense system in order to ensure clear excess free radicals. the body produces free radicals and removal is in a state of dynamic equilibrium. With aging, the body antioxidant defense system hypothyroidism, causing accumulation of free radicals and oxidative stress damage.Seroxide dismutase(SOD) widespread in the biological world, is an important antioxidant in vivo defense oxidative damage, also is an important scavenger of ROS to protect cells from free radical damage. In1938, Mann and Keilin were the first one who diseovered superoxide dismutase(SOD)isolated from bovine red blood cells.In1969,Mccord and Fridovich found this protein had function of catalyticing superoxide anion and disproportionation. The main function of SOD superoxide dismutase catalytic Superoxide anion to hydrogen peroxide and oxygen, and hydrogen peroxide enzyme catalytic Hydrogen peroxide to form H2O2and oxygen. which balance the oxygen free radicals, avoiding damage from excess superoxide anion radical concentration.Malondialdhyde (MDA) is the main product of polyunsaturated fatty acids.The main source of MDA in biological samples is the peroxidation of polyunsaturated fatty acids with wo or more methylene-interrupted double bonds. Excessive MDA with proteins, nucleic acids and other molecules to form lipofuscin deposition in the cell, this is an important reason leading to cellular senescence. At the same time, it can also react with phospholipid protein, changing the permeability of cell membrane, causing tissue damage. MDA is a toxic product of lipid peroxidation metabolism, its content is directly reflected in the rate of lipid peroxidation. Therefore, MDA is often used as a judgment index of damage by free radicals, lipid peroxidation as evaluation indexes.The vascular endothelial become dysfunction and its induced endothelium dependent vasodilation function in the process of aging. Excessive ROS will cause abnormal function of vascular endothelium cell in the process of vascular aging, which promote the occurrence of coronary artery disease. Endothelial nitric oxide synthase is mainly expressed in vascular endothelial cells, it is the maintenance of vascular tone, control of blood pressure, anti atherosclerosis and so on. eNOS is a key enzyme in endothelial derived NO generated, endothelium derived NO plays an important role in maintain the normal function of endothelial cells. In addition, the endothelium derived NO can inhibit platelet aggregation and adhesion in the vessel wall, so as to prevent the formation of thrombus. Endothelium derived NO also has anti atherosclerosis effect, it can inhibit inflammatory cytokines, the apoptosis caused by excessive reactive oxygen species. It also can inhibit the proliferation of vascular smooth muscle cells. Which plays an important role in slowing progression of atherosclerosis and fibrous plaque formation.Statins are hydroxymethylglutaryl coenzyme A reductase inhibitors (HMG-CoA), which reduces the synthesis of methyl valerate through inhibition of HMG CoA reductase, thereby reducing cholesterol levels. Recent studies have found that effects of statins can not only use its lipid-lowering effect to explain. More and more studies indicate that there are many other functions besides the lipid lowering function. Including the effect of reducing oxidative stress, improve endothelial function, anti thrombosis, inhibition of vascular inflammation, plaque stabilization. We call it the pleiotropic effect of statins. There is still not much research about the effects of atorvastatin on oxidative stress and endothelial function in ageing. Therefore, male Wistar rats were subject to the natural aging animal model for the study of aging. To study the effect of atorvastatin on oxidative stress and endothelial function in aging animal model.ObjectivesMale Wistar rats were subject to the natural aging animal model for the study of aging. To study the effect of atorvastatin on oxidative stress and endothelial function in aging animal model.MDA, SOD and eNOS were detect by modern molecular biology.MethodsThe experimental animal and grouping:Altogether3groups of male Wistar rats were involved in this experiment:group of12months old rats, n=8; group of18months old rats, n=8; atorvastatin intervention group(18months old; n=8,5mg·kg-1·d-1atorvastatin were added everyday in diet after12months old). Method of colorimetry for SOD activity and MDA level.The content of eNOS in the thoracic artery was detected by Western blot.All analysis was performed with the use of SPSS software version13.0. The measurement data were expressed as mean±standard deviation. Comparison between groups with LSD test or Dunnett’s T3test. When P<0.05, the difference has statistics significance.Results1.The effects of atorvastatin on malonyldialdehyde (MDA) of the rat artery during aging.Compared with group of12months old rats, the18months group has a higher level of MDA (P<0.01). Compared with group of18months old rats, there is a lower level of MDA in atorvastatin intervention group (P<0.01)2.The effects of atorvastatin on superoxide dismutase(SOD) of the rat artery during aging.Compared with group of12months old rats, the18months group has a lower level of SOD (P<0.01). Compared with group of18months old rats, there is a higher level of SOD in atorvastatin intervention group (P<0.01).3.The effects of atorvastatin on endothelial nitric oxide synthase (eNOS) of the rat artery during aging.Compared with group of12months old rats, the18months group has a lower level of eNOS (P<0.01). Compared with group of18months old rats, there is a higher level of eNOS in atorvastatin intervention group (P<0.01)Conclusions 1. Aging is accompanied by significant changes of antioxidative function in rat artery, including decreased of SOD level, increased of MDA level. Atorvastatin is able to improve the age related of decreased antioxidative function.2. Aging is accompanied by endothelial dysfunction, and eNOS protein expression is decreased. Atorvastatin can improve the endothelial dysfunction and retard the progression of vascular aging, play an important role in preventing cardiovascular diease. |
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