Pm <sub> 2.5 </ Sub> Caused By Coronary Atherosclerosis Possible Mechanism Of The Rat Acs And Atorvastatin Intervention Effect

Part 1 Establishment of Coronary Atherosclerosis Model in RatObjective:To explore the influencing factors of the establishment of coronary atherosclerosis model in rat,3 methods for establishment of the model were compared.So we can establish a matur and reproducible experimental model,which will be a foundation of animal model for investgating the effective of(Particulate Matter)PM₂₅on coronary heart disease.Method:32 Wistar rats were divided into 4 groups randomly.The rats in control group were feed with basic food.The rats in other 3 model establishment grooups were feed with different high fat diets:yolk group(10%egg yolk,10%leaf fat,5%sugar,0.5%sodium cholate, 0.2%propylthiouracil,74.3%basic food),cholesterol group(4%cholesterol,10%leaf fat,5% sugar,0.5%sodium cholate,0.2%propylthiouracil,80.3%basic food),cholesterol group without propylthiouracil(4%cholesterol,10%leaf fat,5%sugar,0.5%sodium cholate,80.5%basic food), and at the beginning 3 days they were injected with V_D320 pan-IU·kg^-1·d^-1.The rats in control group were given saline instead.Record the body weight of rats every week.After 12 weeks,kill rats and collect blood serum then check the blood lipid index(TC,TG,HDL,LDL),calculate atherosclerosis index(AI),and observe the pathological changes in coronary artery.Results:(1)TC,LDL:cholesterol group＞yolk group＞cholesterol group without propylthiouracil＞control group.(2)AI:cholesterol group＞cholesterol group without propylthiouracil,yolk group＞control group.(3)Typical coronary atherosclerotic plaque was found in cholesterol group,while it was not found in yolk group and cholesterol group without propylthiouracil.(4)The body weight of the rats in the cholesterol group and the yolk group has been increasing slowly since the 4^thweek of made-model,even decreased occasionally.In the end,the body weight of rats in this 2 groups is significantly lower than that in control group and cholesterol group without propylthiouracil.Conclusion:(1)Although there is no atherosclerosis(AS)in rat,it can be used as a AS model after some intervention.(2)Coronary atherosclerosis model can be established in Wistar rats successfully after 12 weeks by feeding with high fat diet consisting of 4%cholesterol,10% leaf fat,5%sugar,0.5%sodium cholate,0.2%propylthiouracil,80.3%basic food,and injection with V_D360 pan-IU/kg at the beginning.(3)The level of blood TC is very important during the course of establishing model.(4)Although propylthiouracil can lower the appetite and body weight of rats,it can increase the blood TC apparently,so it is essential to establish the coronary atherosclerosis model in rat.Part 2 Possible Mechanism of PM_2.5Leading Coronary Atherosclerosis to ACS in RatObjective:To explore a new exposure method of PM_2.5:extract water-soluble components (WSC)and acid-soluble components(ASC)from PM_2.5respectively,and give them to rats by vena caudalis injection.To investigation the heart toxicity effect of WSC and ASC on coronary atherosclerosis rats,and the intervention effects of atorvastatin.Method:Rats were divided into 3 groups randomly:control group,model group and treatment grooup.Coronary atherosclerosis model was made on model and treatment groups, according to the above way.At the same time,the rats in treatment group were treated with atorvastatin(10 mg·kg^-1·d^-1)by gastric cube,while the other 2 groups using N.S..Extract WSC and ASC from PM_2.5.12 weeks later,WSC and ASC were given to the rats by vena caudalis injection,and PM_2.5suspension was given by broncho-injection.24 hours later,kill them,and check the serum indexs(blood-fat,MDA,SOD,IL-6,TNF-α,hs-CRP,ox-LDL,NF-κB)by different methods(chemical method,radio-immunity assay,enzyme linked immunosorbent assay,histochemical method,electrophoretic mobility shift assay).Results:(1)WSC can increase the level of TC,AI,TNF-α,and activate NF-κB.(2)ASC can increase the level of TC,TG,LDL,MDA,decrease the level of SOD,and activate NF-κB.(3) There are interaction between coronary atherosclerosis model and WSC,ASC,in increasing the level of LDL,AI,IL-6,and activating NF-κB.(4)In the atorvastatin treatment group,the level of TC,LDL,AI,MDA,SOD,ox-LDL,BP and the activation of NF-κB were improved.Conclusion:(1)The method of treating rats with WSC and ASC by vena caudalis injection is feasible for the investigation of PM_2.5.(2)The heart toxicity effect of PM_2.5on coronary atherosclerosis rats mainly are in 3 aspects:elevating blood lipid,oxidative stress injury,and aggravation of inflammatory reaction.(3)The heart toxicity effect of WSC is to aggravate the inflammatory reaction of body.(4)ASC can aggravate oxidative stress injury and body inflammation interaction.(5)Coronary atherosclerosis model can increase the heart toxicity effect of PM_2.5.(6) Atorvastatin can decrease the heart toxicity effect of PM_2.5on coronary atherosclerosis model. Part 3 Intervention Effects of Atorvastatin Single and Combined Treatment on Coronary Atherosclerosis Rat ModelObjective:To tudy the anti-atherosclerosis effect of atorvastatin single or combined with clopidogrel,losartan,carvedilol on coronary atherosclerosis rat model.Method:Establish coronary atherosclerosis rat model for 12 weeks,and give them different treatments by gastric cube for 8 weeks.The different treatments are:atorvastatin(10mg·kg^-1·d^-1), clopidogrel(25mg·kg^-1·d^-1),losartan(20mg·kg^-1·d^-1),carvedilol(20mg·kg^-1·d^-1),atorvastatin+ clopidogrel,atorvastatin+losartan,atorvastatin+carvedilol.Check the indexs before and after treatment.Results:(1)After the therapy of atorvastatin,the level of TC,TG,LDL,ox-LDL,TNF-α, hs-CRP,and the activation of NF-κB decreased significantly.(2)Combining with clopidogrel, atorvastatin have more effects,such as decreasing MDA,IL-6,and increasing SOD.In addition, there are synergistic action for increasing SOD and decreasing hs-CRP.(3)Combining with losartan,atorvastatin can decrease IL-6,BP,increase SOD,and there is synergistic action for decreasing the activation of NF-κ3.(4)Combining with carvedilol,atorvastatin can decrease MDA,increase SOD,and there is synergistic action for decreasing AI and MDA.Conclusion:(1)Atorvastatin have the effect of anti-atherosclerosis,including lower blood lipid,anti-inflammatory and anti-oxidate.(2)When combining atorvastatin with clopidogrel,it can strengthen the function of anti-inflammatory and anti-oxidate.(3)When combining atorvastatin with losartan,it can strengthen the function of anti-inflammatory and lower pressure. (4)When combining atorvastatin with carvedilol,it can improve the function of anti-oxidate.