|
Arteriosclerosis is a class of diseases characterized by the arterial wallhardening and thickening, luminal stenosis, which is divided intoarteriolosclerosis, middle arterial calcification and atherosclerosis of the threetypes from pathology. Atherosclerosis is the most common and important type,whose characteristic based on the damage of arterial intima, deposition oflipids and complex carbohydrates, secondary fibrosis, leading to arterial wallthickening and hardening and luminal narrowing, thereby affecting the bloodsupply. The common clinical myocardial infarction, cerebral infarction,intermittent claudication are all the result of atherosclerosis. With theimprovement of people’s living standard, the acceleration of population aging,the incidence rate of atherosclerosis in China increased gradually, which hasbecome one of the major diseases that endanger human health. The exactmechanism of the formation of atherosclerosis is not very clear, there areoxidative stress theory, lipid infiltration theory, the damage reaction theory,platelet aggregation and thrombosis theory, inflammation, vascular smoothmuscle cell clone theory, but the oxidative stress theory is one of the basic andclinical research hot spots in recent years. Oxidative stress is the imbalancebetween reactive oxygen species generation and antioxidant of the body whensuffering from a variety of harmful stimuli, causing tissue damage. At present,some clinical trials to the supplement of antioxidant (vitamin C, vitamin E andso on) to prevent atherosclerosis has not achieved the expected clinical effect,The reason may related to not choosing the best antioxidant, application ofantioxidants in a relatively short period of time and the selected populationimproper. Hydrogen, a potential anti-oxidant, have properties ofanti-inflammatory, anti-oxidant, anti-apoptotic, which can play a role of scavenger in cells and organs through selective antioxidant effect. The studymainly investigate the effect of hydrogen-rich water on the prevention andtreatment of atherosclerosis on the basis of rat model of atherosclerosissuccessfully prepared.Objectives: This study aims to establish a simple, economical, repeatableatherosclerosis model,investigate the effect of hydrogen-rich water as selectiveantioxidant on the prevention and treatment of atherosclerosis, and explore theformation mechanism of atherosclerosis.Methods:40Clean and healthy male Sprague-Dawley rats wererandomly divided into4groups: The normal control group, model group,atorvastatin group, hydrogen-rich water group,10in each group. Adaptivefeeding for7days, the normal control group were given normal diet; Modelgroup were given a joint of fat diet, intraperitoneal injection Vitamin D3andpassive smoking; Atorvastatin group were given orally atorvastatin5mg/Kg/don the basis of the model group; Hydrogen-rich water group were given thehydrogen-rich water orally5ml/times,2times/day on the basis of the modelgroup. To eliminate the effects of non-treatment factors on the experiment, thenormal control group was intraperitonealed with physiological saline the sameamount with VD3and gavaged5ml physiological saline BiD; Model groupwas gavaged with5ml physiological saline BiD; Atorvastatin group wasgavaged with the drug dissolved in5ml physiological saline QD and with5mlphysiological saline QD. The experiment lasts12weeks, recording the weightof rats once a week. All rats were blooded in the left ventricle after12weeks,testing total cholesterol (TC), triglyceride (TG), high density lipoproteincholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C);hematoxylin-eosin staining of the ascending aorta, and detecting the8-hydroxy-2′-deoxyguanosine (8-OHdG) of the intima homogenates of thethoracic aortic.Results:①A total of4rats unfinished experiment, among which, modelgroup died2, atorvastatin group and hydrogen water died1separately in their6to7weeks. The cause of death is considered to anorexia, weight loss, poor health.②R at weight change: The weight ofnormal control group increasedsteadily, weighing an average of419±10.33g after12weeks; The weight ofmodel group began to decreased in the first week, weighing an average weightof153.71±6.68g after excluding one extreme12weeks; The weight ofAtorvastatin group and hydrogen-rich water group were no significant changes,the average weight was213.78±15.05g and211.78±12.55g after12weeks.③After12weeks, Lipid test results: blood TC, LDL-C of model groupwere18.20±0.55mmol/L,8.30±0.50mmol/L, which significantly increasedcompared to1.99±0.39mmol/L,0.57±0.25mmol/L in control group (P<0.05);blood TC, LDL-C of Atorvastatin group were3.99±0.46mmol/L,1.48±0.35mmol/L separately, which significantly decreased compared to18.20±0.55mmol/L,8.30±0.50mmol/L in model group (P<0.05), but stillincreased compared to1.99±0.39mmol/L,0.57±0.25mmol/L in control group(P<0.05); blood TC, LDL-C of Hydrogen water group were4.99±0.43mmol/L,1.83±0.23mmol/L separately, which significantly decreased compared to18.20±0.55mmol/L,8.30±0.50mmol/L in model group (P<0.05), but increasedcompared to3.99±0.46mmol/L,1.48±0.35mmol/L in Atorvastatin group(P<0.05); Each group TG, HDL-C showed no significant difference.④In thethoracic aorta membrane tissue,8-OHdG level:8-OHdG of model group was56.80±0.43ng/L, which significantly increased compared to41.18±0.73ng/L incontrol group (P<0.05);8-OHdG of Atorvastatin group47.57±0.42mmol/L,which decreased compared to56.80±0.43ng/L in model group (P<0.05), butsignificantly increased compared to41.18±0.73ng/L in control group (P<0.05);8-OHdG of Hydrogen water group48.39±0.48mmol/L, which decreasedcompared to56.80±0.43ng/L in model group(P<0.05), but increased comparedto47.57±0.42mmol/L in atorvastatin group(P<0.05).⑤Pathological findings,In the model rats,7appeared obvious atherosclerotic plaques; microscopeafter HE staining, endothelial cell loss, intima thickening and protruding intothe lumen, a lot of smooth muscle cell migrated to intimal, fibrous capformation, foam cells and lipid deposition in the intimal, show the typicalcharacteristics of atherosclerotic plaque pathology, part of calcification, little angiogenesis and a large number of inflammatory cells gathering in the outermembrane; The other1had no typical atherosclerotic plaque formation, butunder an optical microscope were seen intima-media thickening, smoothmuscle cell proliferation, derangement, phagocytic cells, a small amount oflipid deposition. Control rats, the structures of all layers of aortic wall werenormal, whose intima smooth, middle membrane elastic fibers arrangednormal; Atorvastatin group showed intima still smooth, medial thickening,smooth muscle fibers arranging slightly disordered, and no atheroscleroticplaque formation; Hydrogen water group showed endothelial still smooth,smooth muscle fibers arranging in a slightly thickened disorder, and noatherosclerotic plaque formation.Conclusions:①A joint fat diet, intraperitoneal injection VD3and passivesmoking, you can create a atherosclerosis in animal models after12weeks,similar to human’s. Atorvastatin can effectively delay the progression ofatherosclerosis, showing that the animal model of the disease is reversible,which can be used in experimental study.②By detecting lipid levels,the8-OHdG of aortic homogenates and the pathology of ascending aorta suggestthat oxidative stress is related to the formation of atherosclerosis.③Thehydrogen-rich water can effectively prevent the formation of atherosclerosis,selectively neutralizing reactive oxygen, which play an anti-atheroscleroticeffect. The therapy of hydrogen-rich water open up a new method for theprevention of atherosclerosis-related diseases.
|