Experimental Study On Effects Of Salvianolate B On Atherosclerotic Plaque Stability

Background: Acute coronary syndrome(ACS) is the emergency in coronary heart disease, Coronary artery atherosclerotic plaque's vulnerablity and instability are the pathological basis of ACS. It is very important that identificating and detecting coronary vulnerable plaques timely and giving effective management for effective prevention of ACS. Coronary heart disease is considered to be a complex diseases of a multi-gene and environment interact. Part of Patients' the traditional risk factors had been controled through treatment and low-density lipoprotein cholesterol (LDL-C) have been significantly reduced in our clinical work, but Coronary Angiography revealed that atherosclerotic plaque continues to progress, which prompted us to look for other coronary heart disease risk factors and new therapeutic targets.Objectives: (1)To set up animal model of atherosclerotic plaque base on balloon-induced abdominal aortic wall injury and high cholesterol diet;(2)To determine blood lipid levels before and after intervention of Salvianolate B and simvastatin; (3)Concentrations of oxidized low-density lipoprotein cholesterol (oxLDL),serum amyloid A(SAA), soluble CD40 Ligand(sCD40L),metalloproteinase-9(MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured by means of Enzyme Linked Immonosorbent Assay (ELISA) to observe effects of Salvianolate B on serum inflammatcory makers;(4)To examine the effect of Salvianolate B on atherosclerotic plaque in rabbits by means of pathomorphology and to explore the relationship of inflammation and atherosclerotic plaque stability and the possible mechanism of Salvianolate B on stabilizing the atherosclerotic plaque. Methods: 40 healthy male New Zealand white rabbits were randomly divided into 4 groups: Salvianolate B group,Simvastatin group, high Cholesterol group and blank Control group.30 rabbits underwent balloon-induced abdominal aortic wall injury and were fed high cholesterol diet(l% cholesterol) for 12 weeks. All the rabbits in the groups underwent pharmacological trigger with Chinese Russell's viper venom(CRVV) and histamine to induce plaque rupture and thrombosis after 12 weeks. Then fasting blood samples were collected for serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride(TG).The concentrations of oxLDL, SAA, sCD40L , MMP-9 and TIMP-1 were measured by means of Enzyme Linked Immonosorbent Assay(ELISA). At the same time, we observed the atherosclerosis plaue of Rabbits in different groups by morphologic methods (Haematoxylin-Eosin staining ) and effects of Salvianolate B on atherosclerotic plaque, the atherosclerosis plaque area were measured by computer graph analysis system.Results: (1) The levels of serum LDL-C and total cholesterol in Salvianolate B group and simvastatin group significantly descreased (P<0.01), TG had no change(P>0.05) in Salvianolate B group. (2)There are lager plaque area in high Cholesterol group,while plaque area of Salvianolate B group and simvastatin group was significantly smaller than of high Cholesterol group (P<0.01) .Compared with simvastatin group,the plaque area of Salvianolate B group had no significant difference (P>0.05). Compared with high Cholesterol group, the value of fibrous cap's thickness divided by thickness of intima and media in Salvianolate B group and simvastatin group was significantly increased,and the value of thickness of intima and media was significantly reduced (P<0.01). (3) The levels of serum oxLDL, SAA, sCD40L , MMP-9 in plaque rupture group and significantly increased (P<0.05) compared with those in plaque non rupture group,serum TIMP-1 had no change(P>0.05). The levels of serum SAA, sCD40L , MMP-9 after rupture group and significantly increased (P<0.05) compared with those before rupture group,serum TIMP-1 had no change(P>0.05). After treatment, the levels of serum oxLDL, SAA, sCD40L , MMP-9 in both Salvianolate B group and Simvastatin group significantly decreased(P<0.05)Conclusions: (1) Salvianolate B could increase the stability of atherosclerotic plaque by specifically changing. The levels of serum oxLDL, SAA, sCD40L , MMP-9 and dereasing break down of matrix collagen and inflammatory reaction. (2) Salvianolate B can decelerate the progression of atherosclerosis. SAA, sCD40L and MMP-9 can be used as reference indices for the identification of plaque instability. (3)Inflammatory makers were significantly higher and get down in the medical group,it may conclude that some inflammatory makers have certain diagnostic value for unstable atherosclerotic plaque. (4) Salvianolate B could lower the level of SAA, sCD40L and MMP-9, in serum significantly alleviate the inflammation of plaque and stabilize the atherosclerotic plaque.