Construction Of Animal Model Of Hemorrhagic Intercourse

ObjectiveTo establish an animal model of TCM theory of endogenous collateral wind " disease which is in accordance with clinical, controllable, repeatable and has easy and wide applicability.MethodsAll male apoE-/-mice were randomly divided into the four groups,including control group,Stress group,Compound48/80 group,Stress+Compound48/80 group.Carotid atherosclerotic lesions were induced by perivascular constrictive collars placement on the right conmmon carotid arteries and proceed syndrome observation in the experiment.Four weeks after surgery,all ApoE-/-mice were injected intraperitoneally with LPS(lmg/kg,Sigma,USA) twice per week for eight weeks.Eight weeks after surgery,mice in Stress group and Stress+Compound48/80 group were administered a restrictive psychological stimulation,four hours every day for four weeks. Ten weeks after surgery,Compound48/80 group and Stress+Compound48/80 group were injected intraperitoneally with Compound48/80.Twelve weeks after surgery,measure the lipid in the blood and made a histological and morphology analyses,including plaque morphology analysis,intra-plaque hemorrhage or plaque disruption,calculating the plaque area,rate of stenosis,lipid, collagenous fiber,Smooth muscle cell,Monocyte/Macrofhage were calculated and plaque vulnerable index were accounted.Result1.Body Weigh:There were no significant differences in the body weights between groups.In total,two mice in Stress+Compound48/80 group died in the experiment.2.Hematology Examination:There wer no significant differences in the lipid profile between groups.3.Histopathological Detection:Rupture rates from Stress+Compound48/80 group were higher than control group(P=0.023).There were no significant differences in rupture between other groups(P>0.05).Intra-plaque hemorrhage rates from Stress+Compound 48/80 group were higher than control group(P=0.043).There were no significant differences in rupture between other groups(P>0.05). There were no significant differences in plaque area, rates of stenosis,lipid and Smooth muscle cell(P>0.05).There were more Monocyte/Macrofhage in Stress+Compound 48/80 group and Compound 48/80 group than in control group(P=0.004,P=0.006).There were no significant diff-erences in collagenous fiber between Stress group and Compound48/80 group (P>0.05),but significant differences in other groups(P<0.01).There were significant differences in plaque vulnerable index between groups(P=0.005).Conclusions1.The animal model was generated by perivascular constrictive collar placement around the carotid artery of high-fat diet ApoE-/- mouse,followed by mental stess, exotoxin and endotoxin co-treatment.It is similar to human obstruction of heartache complex wind in pathogenesis, typical toxic heat syndrome of TCM, which can simulate toxic heat wind disease processes.2.LPS and Compound48/80 co-treatment could promote Intra-plaque hemorrhage.3.LPS and Compound48/80 co-treatment could reduce collagenous fiber.4.LPS and Compound48/80 co-treatment could multiply Monocyte/Macrofhage,and make plaque more vulnerable and easier to rupture.