Effect Of Atorvastatin On Atherosclerotic Plaque Of Carotid Artery And The Expression Of MMP-9 And Hs-CRP In Rats

Background and purposeIn recent years,with the process of aging population in China accelerating,people's living standards and work pressure increasing,the incidence of cerebrovascular disease(CVD)is getting higher and higher,which is bring a heavy burden to families and society by its high recurrence rate,high disability and high mortality.Atherosclerosis(AS)is the pathological basis of cerebrovascular disease.Atherosclerosis can affect the all the blood vessels especially elastic artery,and a large number of clinical trials and animal experiments show that carotid atherosclerosis can represent all the pathological features of atherosclerosis.Increased carotid intima-media thickness(CIMT)is one of the earliest and most sensitive indicators of systemic atherosclerosis [1] and a representative window for the observation of atherosclerotic lesions.The formation of atherosclerotic plaque,falling off and rupture of the vulnerable plaque,aggregation of the platelet and thrombosis is the most important pathogenesis of ischemic cerebrovascular disease [2].At present,the mechanism of atherosclerosis formation is not very clear.There have been some mechanisms be reported such as lipid infiltration theory,oxidative stress theory,theory of inflammation,injury response theory,the theory of thrombosis,platelet aggregation and smooth muscle cell clone theory and so on.With the scholars at home and abroad continue to study,It is thought that atherosclerosis is formed by the above-mentioned multiple factors participating together.And they do a large number of animal experiments and clinical research in order to delay or prevent the formation of atherosclerosis and vulnerable plaque.Statins are currently the most widely used drug which is most effective lipid-lowering,stable atherosclerotic plaque and reverse the atherosclerosis,and Atorvastatin is currently the representative of statins which has the most significant effect and minimal side effects.Conventional-dose atorvastatin(10-20 mg / day)has been shown to be effective in increasing the stability of plaques and reversing the progression of atherosclerosis.Currently,the study of high-dose atorvastatin in the area of prevention and treatment of cerebrovascular diseases has gradually been recognized by people.This study is based on the theory of lipid infiltration,oxidative stress and endothelial injury theory,summarizing the previous experience,through a variety of injury ways to create a simple,practical,economical rat atherosclerosis model,to investigate the effects of atorvastatin at different dosages on atherosclerosis in rats' internal carotid artery.Histopathological changes of atherosclerotic vessels were observed microscopically by dissecting the carotid artery,thus providing a reliable basis for clinical intervention.Materials and MethodsForty-eight healthy adult male Sprague-Dawley(SD)rats were randomly divided into four groups(the control group,the model group,the conventional dose treatment group,the intensive dose treatment group,12 in each group).All the rats were fed with normal diet,after one week,the rats in the model group and the treatment group were fed with high fat diet and administered with vitamine D3 by intraperitoneal injection regularly while the control group was fed with normal diet still.After 14 weeks continuous modeling,blood samples were taken from the tail vein of rats to measure the levels of serum lipid and high sensitive C-reactive protein(hs-CRP).After the rats were killed,take surgical resection of bilateral internal carotid artery 1cm.The histological changes of the internal carotid artery were observed under light microscope,the thickness of internal carotid artery and the pathological changes of atherosclerotic plaque were measured,the number and area of vulnerable plaques were counted,and the expression of matrix metalloproteinase-9(MMP-9)in vulnerable plaques was detected by immunohistochemistry method.To investigate the effects of two doses of atorvastatin on the development of carotid atherosclerosis by the above methods.Results1.Blood lipid:After high-fat diet and atorvastatin therapy,compared with the levels of blood lipids(TC,TG and LDL-C),the level of model group and the two treatment groups were significantly higher than the control group(P <0.01),while the treatment group was significantly lower than the model group(P <0.01).Comparing the two treatment groups,the intensive treatment group was lower than the conventional dose group(P <0.05).2.The level of serum hs-CRP: The level of serum hs-CRP in intensive dose group and conventional dose group was significantly lower than that in model group(P <0.01),and in intensive dose group was lower than that in conventional dose group(P <0.05).The difference has statistically significance.3.Sudan staining and HE staining to observe the pathological changes of the ?internal carotid artery: In control group,the intima of internal carotid artery was smooth and uniform.In the model group and the treatment group,the carotid artery lumen narrowed and the intima thickened obviously,which contained a lot of foam cells and inflammatory cells.The vessel walls became fragile and the elasticity decreased obviously,and obvious vulnerable plaque was seen.There were statistically significant differences among the groups.4.Immunohistochemistry method to detect the expression of MMP-9 in atherosclerotic plaques:The expression of MMP-9 in the carotid artery of the control group detection is negative.The immunohistochemical staining intensity,positive cell rate,and total score of MMP-9 in the conventional dose group was significantly lower than the model group(P<0.05).The immunohistochemical staining intensity,positive cell rate,and total score of MMP-9 in the intensive dose group was significantly lower than the conventional dose group(P<0.05).Conclusion1.Atorvastatin can effectively reduce the level of serum lipid,hs-CRP,and the expression of MMP-9 in atherosclerotic plaque,and play a role in stabilizing and reducing the formation and progression of vulnerable plaque in carotid atherosclerosis.2.In the therapeutic dose,the effect of atorvastatin on regulating blood lipids,stable plaque,reducing vulnerable plaque and reversing intima thickness was positively correlated with its dose.