| Objective:The improvement of living standards and life expectancy will lead to cardiovascular and cerebrovascular diseases caused by atherosclerotic. Pro-gressing of atherosclerosis with age is a cause of vascular occlusive disease, such as myocardial infarction(MI) and cerebral infarction(CI). Although the progress of treatment and treatment guidelines widely application expected to reduce the cardiovascular and cerebrovascular events, but it is still the leading cause of death in patients. The occurrence and process of atherosclerosis(AS) due to the joint of risk factors, and some risk factors increase with lifestyle changing, and the most important risk factor is high cholesterol, soit is need new drugs to manage high cholesterol levels and to prevent atherosclerosis disease. Probucol is a kind of bisphenol compound that contain two molecules antioxidants - butyl toluene(BHT), has the effect of antioxidant and specifically to decreas plasma total cholesterol, prevent cardiovascular events. Atherosclerosis disease includs coronary artery disease, cerebral infarction, arteriosclerosis block disease, and vascular injury associate with these diseases, so,prevention of platelet rupture and platelet thrombus formation after rupture is the key to treat disease. Cilostazol,has the antiplatelet and vasodilation role, and can Protect vascular endothelial cells. Meanwhile probucol and cilostazol can reduce arterial medial thickness (IMT), as a significant inhibition of restenosis after percutaneous coronary angioplasty, and can prevent restenosis after coronary intervention,thereby inhibit the atherosclerotic plaque thrombosis. The two drugs apply alone or in combination can improve the vascular endothelial function,and play role in anti-oxidation and anti-atherogenic to promote atherosclerotic plaque attenuation. With further research, atherosclerosis-related biomarkers participate in the development of the disease, and intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) expression increases in the inflammatory stimulation, and promote endothelial cell damaged, vascular dysfunction,which is leading to the formation of unstable plaques, the level of soluble adhesion molecules in circulating blood may reflect the inflammation state of atherosclerosis. Von Willebrand factor (vWF) level in the plasma is a sensitive indicator of endothelial cell injury and hypercoagulable state ,it is higher in the blood in patients prompting hypercoagulable state, and is the key factor of vessels of atherosclerosis acute occlusion. The Monocyte chemoattractant protein (McP-1), either alone or in combination with other cytokines, can chemotac monocyte and macrophagocyte,and is involved in the process of inflammation and cancer and hematopoiesis and angiogenesis. Under the action of ischemia, hypoxia, inflammatory cytokines,endothelial cells and platelet active,and sP-selectin would quickly transfer to the cell surface, and mediate adhesion among platelets, endothelial cells,and neutrophils, and involve in local microvascular platelet aggregation, activation and infarct formation. The CD40 Ligand drifting on the blood circulation has biological activity, and 95% of sCD40L in blood circulation is from activated platelets, and platelet activation, adhesion and aggregation is the process of arterial thrombosis. CD40L plays an important role in this process . Thrombomodulin (TM) combines both anticoagulant and antifibrinolytic properties,and is released into the blood when vascular endothelial cell is injured, and TM is the reliable indicator of detection of vascular endothelial cell injury. Clinical study found that CRP is a inflammatory cytokines re latead with the evolution and development of atherosclerosis, and high sensitivity C-reactive protein (hs-CRP) ,as the inflammatory marker of atherosclerosis and participating in the pathogenesis of cerebral infarction, is independent risk factor of heart cerebrovascular disease. And interleukin -6 as a major regulator of inflammation medium,which is secreted by vascular endothelial cells and smooth musclecells,acts on the vessel wall damage, participate in the formation and development of atherosclerosis. Oxidized low density lipoprotein (Ox-LDL) is the important risk factors of atherosclerosis, and can enhance monocyte and T lymphocyte adhere to endothelial cells, and promote vascular smooth muscle cell to proliferate, migrate and induce the release of multiple cytokines by inflammatory cells in plaques The urinary 8 - hydroxy-deoxyguanosine (8-OHdG) is a DNA oxidative damage biomarker, can change the nature of base pairing, leading to misreading and DNA mutation, which initiates cell mutation, and causes oxidative stress reaction in the body and promotes cell endothelial injury ,and causes the formation of atherosclerosis. In recent years, studies have shown that lipid metabolism disorder is a risk factor for the atherosclerosis disease,and is a major predictor of severe intracranial stenosis. Lipid metabolism disorder is hematic disease of high cholesterol (TC), high triglyceride (TG), high density lipoprotein (LDL-C) and low high-density lipoprotein (HDL-C).Hypercholesterolemia can produce small, dense low-density lipoprotein, and promote blood clotting, and affect modification of oxidative lipoproteins and other means to promote the formation of atherosclerosis, and hypertriglyceridemia, through affecting the structure of high-density or low density lipoprotein induce atherosclerosis,and can cause vasodilatation is impaired significantly,which is endothelial cell-dependent, while the reduction in the level of high density lipoprotein leads to increased cholesterol of peripheral and causes lipid deposition in vascular wall , and it is the only lipid index of increased risk of ischemic disease, and lipoprotein B is the most valuable indicators for predicting atherosclerotic disease , its level is an important risk factor of atherosclerosis. Taking all these factors, we carry out researching to expand the treatment of atherosclerotic disease and to make secondary prevention medication ideas.Methods: 48 patients of 1 month after infarction to 12 months, aged 40 to 80 years met the inclusion criteria.And using the randomized, controlled, open, multi-center study method, they were divided into four groups Aspirin (A), cilostazol treatment group (B), probucol (C), cilostazol combined probucol (D). Dosing method: the control group Aspirin 100mg1 / day orally after breakfast. Group B: cilostazol 50mg (1 piece) 2 / day, and if is without discomfort after a week then given 100mg (2 tablets) 2 / day, or the maintenance 50mg (1 piece) 2 / day, and record adverse reactions; C : Probucol 250mg (1 piece) 2 / day; D: cilostazol 50mg (1 piece) 2 / day, and if is without discomfort after a week then given 100mg (2 tablets) 2 / day, or the maintenance 50mg (1片) 2 / day, and record adverse reactions, probucol 250mg (1 piece) 2 / day, drugs are orally after breakfast and supper. B, C, D combination treatment group while enteric-coated aspirin tablets 50mg1 / day orally after breakfast. In addition to combination therapy of aspirin, but prohibit other antiplatelet or anticoagulant drugs, in addition to other statins, prohibit the use of other lipid-lowering drugs.Period of 3 months between administration of the test period between 6 months and 5 times (V1~ V5) follow-up, V1 screening of patients in selected hospitals within 2 months of laboratory tests (blood, urine, blood biochemical) results as the research data available(.Ⅴ2~Ⅴ5)follow-up period according to test procedure 1) recording of compliance and patient vital signs (blood pressure, pulse, respiration, body temperature), weight status (Ⅴ2~Ⅴ5).2) The line drawn fasting elbow related biological markers blood test, urine specimens from the parallel electrocardiogram (Ⅴ2~Ⅴ5). 3) The line drawn fasting venous blood after administration elbow plasma concentration of metabolites detected (Ⅴ5). 4) records before and after treatment of clinically significant abnormal laboratory findings, vital signs, physical examination and ECG findings, the recurrence of cerebral infarction, cerebral hemorrhage (V1~V5). 5) V2, V5 laboratory centrifuge blood aside half an hour later, the serum obtained after the seal-packing according to the label, put together with the urine specimens in -20℃refrigerator, and transport to the designated center within two weeks of lab-line-related factors detection. Line statistical analysis software package using SPSS13.0 1) general statistical methods: All data will be applied descriptive statistics, frequency tables, and data analysis and summary list. Before taking measurements as the baseline value. 2) the analysis of categorical variables: Applicating information completely randomized design analysis of variance or more independent samples rank sum test 3) the analysis of continuous variables before and after treatment: paired t test or two related samples to compare rank sum test. (P≤0.05 statistically significant).Results: 174 patients completed in five centers CCP test, and this center has 39 patients completed the final test, in which the control group (A), 9 cases,cilostazol group (B) 8 cases ,probucol group (C) 11 cases, cilostazol combined probucol group (D) 11 cases.And 9 cases were lost,and has nothing to do with the medication about of drug. A group and B group before and after treatment of atherosclerosis-related biomarkers was no significant effect (P>0.05), C group before and after administration of sCD40L and HDL-C was statistically significant (P≤0.05), the other showed no statistical significance, D group before and after treatment on VCAM-1 and TC was statistically significant (P≤0.05), the other showed no statistically significant (P>0.05). Four groups after treatment were no significant difference between groups (P> 0.05). Security Analysis ,there is no serious adverse reaction.Conclusion:1 The test results of the five centers is that the combination therapy is more effective than single drug on controlling and treating voxidized low density lipoprotein (OX-LDL),monocyte chemoattractant protein (McP-1),vascular cell adhesion molecule (VCAM-1).and cholesterol (TC) Safety evaluation: the two drugs alone and combination of two drugs both there are no serious adverse reactions and other adverse reactions.2 The conclusions of the above indicators of voxidized low density lipoprotein (OX-LDL) and monocyte chemoattractant protein (McP-1) in this center is not statistically significant, and it is may be related with the small sample.Probucol used alone is effective on the CD40L ligand (sCD40L) and high density lipoprotein (HDL-C), cilostazol consolidated probucol is effective for vascular cell adhesion molecule (VCAM-1) and cholesterol (TC), but it requires a large sample to be confirmed.Safety evaluation conclusion is as same as that of the multi-center... |
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