Research Alprostadil Injection Intervention Of Atherosclerosis Sclerosis Rat Model

Atherosclerosis (AS) is a serious chronic disease, which is harm topeople’s life and health, the lesion blood vessel local often comes in a varietyof pathological change successively or simultaneously, including sugaraccumulation of lipid infiltration, composite, fiber tissue hyperplasia,calcification and arterial membrane degeneration and so on, in the latehemorrhage often accompanied by plaque, plaque rupture and localthrombosis, etc. Blood supply arteries, AS often happens in vital organs suchheart, brain and kidney arteries, causing corresponding organ ischemicchanges, such AS coronary heart disease, brain stroke, renal artery stenosisand so on.Acute myocardial infarction is caused by the AS, it is one of the mostserious disease and the highest mortality rate, atherosclerotic plaque ruptureand secondary thrombosis is its pathological basis. The drug prevention andtreatment for acute myocardial infarction remains in active exploration, how toestablish a reliable and economic animal model of atherosclerosis, for acutemyocardial infarction and other cardiovascular system disease clinicalresearch is of great significance.The disease is caused by a variety of risk factors for a long time, theresult of joint action, it is certain at present. Different researchers fromdifferent angles to explore the mechanism and has produced many theories,including the endothelial injury or inflammation doctrine recognised by mostscholars, considered AS contain a variety of inflammatory mediators involvedin inflammatory bowel disease, arterial intima is the results of various damagefactor inflammatory response and inflammatory factor directly participate inthe process of and adjust the AS through the whole process, so theanti-inflammatory intervention become one of research focuses in ASprevention and treatment. Malondialdehyde (MDA) is an inflammatory oxygen free radicals to stimulate the body lipid peroxidation of lipid peroxides,it reflect the content of the body lipid peroxidation and the degree ofinflammation, indirectly reflect the degree of cell damage, inflammation isnow commonly used oxidation index.Objective: This experimental research attempt to establish a reliablemethod in atherosclerosis rat model through a new method, which is simpleand economy, and observation of alprostadil injection to the intervention ofthe atherosclerosis in rat model to explore its action mechanism.Methods: Totle40sprague Dawley (SD) rats,male,7-8weeks old,weighed180~220g, all rats were fed with normal diet1week. Then dividedinto four groups by completely random sampling of the original,there are10rats in each group: normal control group (A group), model group (group B),alprostadil intervention group (Group C), atorvastatin group (group D). Sincethe beginning of the second week,the rats of group A were fed a normal dietcontinued to13weekends, and during the experiment without anyintervention;the rats of group B were given the high fat forage+intraperitoneal injection of large amounts of vitamin D3+passive intervention;rats of group C were given alprostadil injection intervention on the basis of thehigh fat forage+intraperitoneal injection of vitamin D3+passivesmoking,alprostadil injection will be in0.9%sodium chloride injection to20ml by5ug/kg.d intraperitoneal injection of administration12weeks, rats ofgroup D were given atorvastatin intervention on the basis of the high fatforage+intraperitoneal injection of vitamin D3+passive smoking,atorvastatin calcium tablets will be crushed by5to20ml mg/kg.d gavageadministration of12weeks. Pharmacological interventions are carried outdaily in the afternoon, all rats adequate daily feed supply free drinking water.After dissecting the rats completed the intervention, in the apical portion of theleft ventricle blood2-3ml, detecting blood triglycerides (triglycerides,TG),total cholesterol (total cholesterol,TC), high density lipoprotein cholesterol(high-density lipoprotein-cholesterol,HDL-C), low-density lipoproteincholesterol (low-density lipoprotein-cholesterol,LDL-C) concentration and determination of serum inflammatory markers oxidation of MDA. Carefullypeel off the aorta, the aortic root to take2-3cm of vessels, with4%paraformaldehyde, conventional dehydration, including wax, sectioned andstained using hematoxylin-eosin staining and light microscopy aorticpathology change and contrast in each experimental group intervention modelto determine the situation and be prepared alprostadil injection.Results:1This experiment adopts the high fat forage+intraperitoneal injection ofa large number of vitamin D3+passive smoking, the method of atherosclerosisrat model was established successfully, there are40rats in this experiment,survival36, four rats dead, death time is7and8weeks,2rats in model group,1rat in the alprostadil intervention group, and1rat in atorvastatin group, thecause of death may be linked to rats decreased appetite, poor resistance,diarrhea and so on.2Blood lipid test results: the levels of serum TC(mmol/L) and LDL-C(mmol/L) of group A were2.04±0.39,0.59±0.26; group B were18.20±0.55,8.29±0.49; group C were3.96±0.32,1.47±0.15; group D were3.99±0.46,1.48±0.35. Levels of serum TC, LDL-C comparison between the two groupsA and B, P values <0.05, group B were higher than that of group A; levels ofserum TC, LDL-C comparison between the two groups B and C, P values <0.05, group B were higher than that of group C; levels of serum TC, LDL-Ccomparison between the two groups B and D,P values <0.05, group Bwere higher than that of group D; between the group C and D, P values>0.05,no difference between group C and D; between the group A and C,P values<0.05, the levels of serum TC, LDL-C of group A were higher than group C;Comparison between A and D,P values <0.05, levels of serum TC, LDL-C ofgroup A were higher than group D.3MDA test results: The levels of serum MDA (nmol/mlprot) in A, B, C,D four groups were0.032±0.010,0.489±0.019,0.051±0.010,0.055±0.013.comparison between group A and B, P value <0.05, serum MDA level ofgroup B higher than that of group A; comparison between group B and C, P value <0.05, serum MDA level of group B higher than that of group C;comparison between group B and D, P value <0.05, serum MDA level ofgroup B higher than that of group D; comparison between group C and D, Pvalue>0.05, no difference between group C and D; comparison betweengroup A and C, P value <0.05, serum MDA level of group A of is higher thanC group; comparison between group A and D, P value <0.05, serum MDAlevel of group A higher than that of group D.4Histopathological changes: Ordinary optical microscope pathology ratsin each group were prepared model success rate of70%. Group A: rat aorticintimal smooth endothelial integrity and middle endometrial cells arrangedrules, a clear outline of the surrounding cells, middle and smooth and white,arranged in neat rows. Group B: the wall of visible aortic is not smooth,continuous endothelial damage, intimal hyperplasia, hypertrophy, wrinkled.Thickening of the membrane, the cell membrane morphology varied,disorganized loose, cell gap widened, visible fat cells and smooth muscle cellsmigrate to the inner layer. Group C: in rat aorta smooth muscle cell membranemild hyperplasia, compared with the model group arranged neatly, no foamcell formation, endothelial damage lighter, more normal vascular tissuestructures. Group D: rat aortic intima intact endothelium no obvious damage,the film endometrial cells arranged in neat, no large amounts of foam cellformation, organizational structure has been basically normal. Compared withthe model group and the treatment group(included alprostadil interventiongroup and atorvastatin group), the treatment group atherosclerosismorphological changes significantly reduced, as demonstrated in rat arterialintima drug treatment group was significantly reduced proliferation of smoothand without projections and folds middle reduce smooth muscle cellproliferation, inflammatory cell infiltration reduced.Conclusion:The study select the high fat forage+intraperitoneal injection of vitaminD3+passive method for preparing a rat model of AS by learn from the pastand strengthen multiple risk factors intervention. AS is confirmed by multiple risk factor in the long-term result of the role, high-fat diet, a lot of vitamin D3,passive smoking are on the starting role in promoting the formation of AS.Alprostadil injection can be adjusted dyslipidemia section AS rats, delayingthe progress of the inflammatory response, reducing the severity of AS rataorta, inhibit the formation and development of atherosclerotic plaques,vascular stenosis reduced intimal smooth muscle cell proliferation and toreduce inflammation cell infiltration was significantly reduced. Atorvastatincan regulate blood lipid disorders, slow the progress of atherosclerosis,reduced aortic lesions, the experimental results of this study concluded.