Effects Of Tanyu Tongzhi Prescription On Rabbit Atherosclerosis Model

Cardiovascular disease is the world's first death cause of human.The principal pathological basis of coronary heart disease,stroke and other cardiovascular diseases is atherosclerosis(AS). For different AS animal models have various advantages and disadvantages,it is necessary to choose the model for the mechanisms of AS research and drug intervention.At first the subject use three different methods to establish rabbit AS model(simple Balloon-Injured,simple Cholesterol, Composite factors),and then comparing the characteristics of three methods.Investigate lipid metabolism,PON-1 activity,plasma Hcy concentration,the level of inflammatory factors and the extent of aortic plaque formation in the models.Through the comprehensive analysis the model prepared from Composite factors was considered the best one.On the base of the established model prepared by Composite factors model,this article also observed the therapeutic effects of Chinese herbal prescription-Tanyu Tongzhi1.Establishment of the atherosclerosis model in rabbits1.1 Materials and methodsSelected rabbits were randomly divided into 4 groups:(1) normal control group(Control,Con): normal diet without aorta injury,n=6;(2) simple balloon injury group(Balloon-Injured,BI): normal diet,aortic injury,n=6;(3) simple high-fat group(Cholesterol,Cho):high-fat diet without aortic injury n=6;(4) composite factor model group(Composite,Com):aortic injury and high fat diet,n=6.At the beginning of the experiment,a 3F Fogarty embolectomy catheter was inserted into the artery,and then withdrawn from thoracic aorta to abdominal aorta origin with the balloon inflated to 0.2 ml saline,a step repeated there times(30 seconds per time).1.2 Results1.2.1 Lipid metabolism Four weeks after artery injury,the total cholesterol(TC),and low density lipoprotein(LDL-C) in high-fat diet group of Cho and Com group were significantly increased compared with those of Con group(P＜0.01).No significant statistical difference was observed between BI group and Con group.1.2.2 Serum PON-1 activity At the end of 12 weeks,Cho and Corn groups demonstrated lower level of PON-1 activity than Con group(P＜0.01).There was no statistical difference on between BI and Con group.1.2.3 Plasma Hcy concentration At the end of 12 weeks,plasma Hcy concentration in Com group was markedly increased than that of Con group(P＜0.01).BI and Cho Group Hcy concentrations were also increased,but there were no statistical differences compared with the Control.1.2.4 Inflammatory factors At the end of 12 weeks,BI and Cho group CRP,IL-6, TNF-α,sCD40L,MMP-9 level of inflammatory factors were increased,but there were no statistical significance.And for Com Group,the inflammatory factors levels was markedly increased than that of the Con group(P＜0.01).1.2.5 Aorta changes At the end of 12 weeks,no plaque formation of blood vessels was determined by SudanⅢstaining in Con group and BI group,But in Cho and Com Group typical AS plaque was observed with(44±15)%and(74±13)%respectively.1.3 ConclusionThe three model approaches employed in the paper showed different effects on lipid metabolism,PON-1 activity,Hcy concentration,inflammatory factor levels and vascular pathological changes.Among the three model approaches,the Composite factors(Com) rabbit model showed dramatic impacts on the above changes.Composite factor model integrated the advantages in both simple balloon injury(BI) and high-fat diet(Cho).The model not only corresponded with the process of the atherosclerosis evolution,but also can be used as a AS model for drug evaluation.2.Effect of Tanyu Tongzhi prescription on rabbit atherosclerosis model2.1 Materials and methodsThe model preparation and other concerned methods were as the same as the part 1.1.After the aortic injury animals were divided into 6 groups:(1) normal control group(Control,Con);(2) model group(Model,Mod);(3) simvastatin group(Simvastatin,Sim):simvastatin 2mg/Kg;(4) Tanyu Tongzhi prescription 5g/kg dose group(TYTZ 5g/kg);(5) Tanyu Tongzhi prescription 2.5g/kg dose group(TYTZ 2.5g/kg);(6) Tanyu Tongzhi prescription 1.25g/kg dose group(TYTZ 1.25g/kg).High fat diet group of rabbits were fed high fat diet in the beginning until the end of the experiment.At the end of 4 weeks,groups of the treatment rabbits were administered orally respectively until the end of the experiment(12weeks).2.2 Results2.2.1 Lipid Metabolism The serum TC and LDL-C level TYTZ5g/kg and 2.5g/kg dose group were significantly decreased compared with model group(P＜0.01).2.2.2 Serum PON-1 activity TYTZ of each dose could increase the serum PON-1 activity. Among them the significant difference could be observed in 5g/kg and 2.5g/kg dose group (P＜0.01 and P＜0.05).2.2.3 Plasma Hcy concentration TYTZ of each dose could reduce plasma Hcy concentration. Among them the significant difference could be observed in 5g/kg dose group(P＜0.01).2.2.4 Inflammatory factors TYTZ of each dose could significantly reduced the levels of inflammatory factors(P＜0.01 or P＜0.05).There was no statistical difference among each dose group.2.2.SAorta changes TYTZ could reduce the plaque formation of blood vessels.There was significant difference between TYTZ 5g/kg dose group and Mod group(P＜0.01)2.3 ConclusionTYTZ might play an anti-atherogenic role by regulating lipid metabolism,restoring PON-1 activity,reducing Hcy concentration and anti-inflammatory activity.