Experiment Study On Effects Of Tongxinluo Capsule On Atherosclerotic Plaque Stability

Background No matter in developed countries or developing countries, coronary heart disease (CHD) is one of the most common diseases leading to deformity or even to death. Therefore it becomes urgent to prevent from CHD Effectively over the world. In the meantime, the clinic studies in CHD get quicker development, especially the rising of "medicine based of evidence pour tremendous vitality into the clinic study and basic study in CHD. Acute coronary syndrome(ACS) is the emergent syndrome in CHD, which covers a range of clinical pathophysiological condition, from unstable angina pectoris (UAP), acute myocardial infarction(AMI) , sudden death and so on Along with the deep-going of the research, as is known, on the basis of coronary artery atherosclerosis, plaque disruption and thrombosis is the main pathophysiological base in the CHD's emergency, especially in the ACS. The episode of ACS is not mainly caused by a stenosis but caused by the rupture of an unstable plague and the subsequently thrombus formation. Many factors can causethe plaque's instability Such as the size of lipid core, the thickness of fibrous cap and the content of collagen and so on. .To some extent, factors which influence the plaque's stability must also influence the clinic symptoms and prognosis of CHD. Coronary artery rebuilding alleviate its stenosis, but did not obviously release theincidence of ACS compared to medication, unstable plaque is the main reason, so it is very important to understand the internal characteristic ,rupture mechanism, indentify method of unstable plaque and search for the methods of stabilization plaque.Objective (l)To set up animal model of atherosclerotic unstable plaque (2)To observe the effect of Tongxinluo capsule on blood morphologic and plaque pathologic condition by intravascular ultrasound (IVUS) (3)To determine the plasma levels of MMP-1 and TIMP-1 by means of immunohistochemistry to observe the effect of Tongxinluo capsule on matrix metalloproteinase(MMP-l) and tissue inhibitor of metalloproteinase(TIMP-l) (4)concentrations of hsCRP ,P-selection and MMP-1,TIMP1 were measured by means of Enzyme Linked Immonosorbent Assay(ELISA) to observe the effect of Tongxinluo capsule on serum inflammatory makers(5)To examine the effect of Tongxinluo capsule on atherosclerotic plaque in rabbits and to explore the possible mechanism on stabilizing the atherosclerotic plaque .Methods 46 healthy male new Zealand white rabbits underwent ballon-induced abdominal aortic wall injure and were fed high cholesterol diet(l% cholesterol) for 8 weeks .8 weeks after the initiation of the diet , 16 rabbits were take out from the rabbitsd as A group . The rabbits in the A group underwent pharmacological triggering with Chinese Russell'svip ervenom(CRVV) and histamine to induce plaque rupture and thrombosis .By comparing the results of IVUS, rabbits were divided into 2 groups :the plaque ruptured group and plaque non ruptured group, the level of Inflammatory makers such as P-selection hsCRP,MMP-l were measured .The surviving rabbits were randomized into 3 groups :Tongxinluo group(n=10), normal diet group(n=10) and group HL (n=10) .Then all the rabbits in the groups underwent pharmacological trigger after 12 weeks. After experiment, fasting blood samples were collected for serum TC, HDL-C, LDL-C, TG, and Fib Assay. The concentrations ofhsCRP ,P-selection and MMP-1 were measured by means of Enzyme Linked Immonosorbent Assay(ELISA). IVUS was used to observe changes about blood morphologic and plaque pathologic condition, the levels of MMP-1 and TIMP-1 was determine by means of immunohistochemistry.Results (1) The levels of serum hs-CRP , MCP-1, IL-8, IL-18, MMP-1, P-selectin in plaque rupture group significantly increased (P< 05)compared with those in plaque non rupture group(P<0.01,respectively),serum IL-10, TIMP-1, MMP-3, MMP-12 had no change.(2)After treatment, the levels of serumMMP-l.hsCRP and p-selectin in both tongxinluo group and normal diet group significantly decreased(P<0.05),the levels of serum TC,TG,LDL-C in treatment significantly reduced (P<0.05)and those of serum TC,LDL-C reduced(P<0.05),TQHDL-C had no change(P>0.05).The Immunohistochemistry showed there are more positive cells of MMP-1 in the normal diet group and group HL . and positive cells of TIMP-1 had no change in three group.there were no significant difference between tongxinluo group and normal diet group.EEMA, plaque area in the tongxinluo group were smaller than those of normal diet group and group HL(P<0.05 WL PO.01 ).And lumen area narrowing rate in the tongxinluo group were smaller than that of group HL ( PO.05 ) , there were no significant difference between tongxinluo group and normal diet groupConclusions (l)Tongxinluo could increase the stability of atherosclerotic plaque by specifically changing the local expression of MMP-1 and dereasing break down of matrix collagen and inflammatory reaction. (2)Tongxinluo can decelerate the progression of atherosclerosis. MMP-1 and TIMP-1 can be used as reference indices for the identification of plaque instability. IVUS can detect unstable atherosclerotic plaques and predict plaques disruption in early stage of atherosclerosis using our animal models of unstable atherosclerotic plaques. (3)Inflammatory makers is significantly higher and get down in the follow-up group,it may conclude that some inflammatory makers have certain diagnostic value for unstable atheroscleroticplaque.(4)tongxinluo could lower the level of P-selection hsCRP,MMP-l,in serum significantly alleviate the inflammation of plaque and stabilize the atherosclerotic plaque. (5)plasma fibrinogen level were one of the main risk factors of atherosclerosis . Fibrinogen may play an active role in development and progression of atherosclerotic plaque.