The Clinical Research Of The Effect Of The PAS Theropy To Atherosclerosis Patients.

Background:Atherosclerosis(AS)began in childhood and continued pro-gress,usually it shows clinical symptoms in the middle-aged or in the late-middle-aged. Dyslipidemia,smoking,hypertension,hyperglycemia,reduced physical acti-vity,genetic factors,age,sex,alcohol intake and excessive,and many other factors are considered as atherosclerosis risk factors.The disease has shown clinical symptoms of multiple factors,which is the result of the multiple roles. First of all,it is the result of the aggregation of the smooth muscle cells, macrophages and T lymphocytes in the pathological changes area;followed is the proliferation of collagen,elastic fibers and protein and polysaccharide, other connective tissue matrix,and the smooth muscle cells;and the third is lipid,which mainly contains free cholesterol,cholesterol crystal cells,and connective tissue accumulation.The content of the lipid and connective tissue decides the stability of atherosclerotic plaque and the ischemia incidents.The smaller the atherosclerotic plaque lipid nuclear,the thicker the fibrous cap,the more collagen fibers,the more smooth muscle cells,the less the matrix metalloproteinases,macrophages,the less the foam cells,the more stable the atherosclerotic plaque is;otherwise the less stable the atherosclerotic plaque is. Atherosclerosis contains the pathological changing process of stability and instability.Unexpected and unforeseeable cardiocerebral vascular events have relation to the plaque rupture.Plaque rupture includes active,passive and plaque rupture erosion.Active rupture is the result of digestion of fibrous cap,which is due to the protease excreted by the monocytes and macrophages.The passive rupture is caused by the outer forcing to the weak parts(usually at the thinnest parts of the fibrous cap or at the junction of the normal vessel walls)of the fibrous cap.And the plaque erosion is more often in women.After plaque rupture or erosion,the thrombosis adheres to plaques in the surface.After the rupture of the plaque,the thrombosis entered into the plaques,and then led the luminal stenosis rapidly,and finaly led to the occlusion of the lumen incompletely or completely.Atherosclerosis is a continuous thrombosis of the overall disease and a systemic diseases.To sum up, to make the atherosclerotic plaque stable is the key to the treatment of atherosclerosis,while with the hope of the reversing or reducing the plaque. Although there are a variety of factors which can cause plaque instability, while animal experiments and clinical trials have proven that the increased levels of MMPs played an important role in the plaque instability.Research has proved that coronary atherosclerotic disease death is the mainly caused by acute myocardial infarcttion,and 90%of patients with acute myocardial infarction is caused by plaque rupture,while the main factor leading to plaque rupture is the role of MMPs.The clinical researches have proven that probucol has obvious inhibiting role to MMPs,so we consider that when treating atherosclerotic diseases,in addition to the recognized intensive lipid-lowering therapy from the substance reducing to block the formation of lipid nuclear, blocking the LDL oxidized also may be a new therapeutic concept.In addition, the expansion of narrow arteries and preventing the thrombosis after atherosclerosis plaque rupture or erosion,has no doubt become an important component part to atherosclerosis treatment.Nitrate drugs and aspirin has been recognized having the above two roles in theory and clinical practice,and has been considered as the essential drugs in the treatment of coronary heart disease.Therefore,the PAS therapy,which is based on the regulating lipid, expansion artery stenosis,anti-platelet aggregation,and other traditional treatment,plus having the antioxidant role of the matrix metalloproteinase inhibitor-Probucol,has become the necessary treatment of atherosclerosis in theory.Experimental purposes:1.The two groups were observed in patients with coronary heart disease, one group was given the traditional regulating lipid,extended crown, anti-platelet aggregation therapy,and the other group was given PAS(on the basis of conventional therapy plus Probucol),two months after the treatment, Statistics were taken from the two groups of patients with clinical manifestations and pro-MMP-2,MMP-2,ox-LDL,TXB2,TIMP changes, with the hope that PAS therapy is better than the traditional therapy according to the above indicaters.2.Give the patients suffering from peripheral artery atherosclerosis the PAS therapy for two months,and then take the results of statistical and clinical manifestations and the changes of pro-MMP-2,MMP-2,ox-LDL, TXB₂,TIMP,with the hope of after the PAS theropy,we could draw conclusions that the patients have significantly improved at the aspect of clinical symptoms and at the corresponding examinations.Experimental Methods:1.Collecting patients from July 2007 to December 2007 hospitalized with coronary heart disease,observe their clinical manifestations and the changes of pro-MMP-2,MMP-2,ox-LDL,TXB₂,TIMP.2.To the peripheral artery atherosclerosis patients admitted from March 2007 to December 2007,determine the results of clinical diagnosis and rule out infection in accordance with peripheral arterial vascular CDFI,peripheral arterial angiography and pathologic diagnosis in the surgical process,and finally we collect 4 patients.Give lipid(atorvastatin,20 mg,oral,once a day), anti-platelet aggregation(baiaspirin,100 mg,oral,once a day),antioxidant (Probucol,250 mg,oral,twice a day),the treatment lasted for two months.The results:1.PAS group patients with angina and coronary heart disease of the ECG efficiency is better compared with conventional therapy group,and there were significant differences(P＜0.05).2.The result from PAS group patients before treatment is:pro-MMP-2 (13065±11027)INT·mm-2,MMP-2(4654±2523)INT·mm-2,two months after the treatmentis:pro-MMP-2(11,114±10,037)INT·mm-2, MMP-2(3432±2439)INT·mm-2;The result from traditional therapy patients before treatment is:pro-MMP-2(10,688±8275)INT·mm 2, MMP-2(5917±6137)INT·mm-2,two months after the treatment is: pro-MMP-2(7898±4588)INT·mm-2,MMP-2(4899±4874)INT·mm-2. The two indicators of the two groups patients before treatment were higher than normal,two months after the treatment,the two indicators have improved,compare the pro-MMP-2 and MMP-2 in the serum of the two groups respectively before and after treatment,there were significant differences(P＜0.05)of the PAS therapy patients before and after the treatment,while the pro-MMP-2 and MMP-2 from the traditional therapy group after treatment had improved than before,but without statistical significance.Figure 1-2 shows the gel electrophoresis results,Figure 3-6 shows the numerical change with these two indicators of two groups before and after treatment.3.The results of TXB₂ and ox-LDL levels in the serum were higher than the normal average of the two patients with coronary heart disease,but without constituting a multiple relations,while the TIMP leval is lower than the normal average,.After two months treatment,ox-LDL and TXB₂ show downward trend,while TIMP leval shows an upward trend,but withouty statisticcally significant(P＞0.05).4.After PAS therapy,four cases of peripheral artery atherosclerosis patients have thier clinical symptoms and signs improved markedly.Only one case of patients with vascular CDFI result is improved significantly,and the other three patients with vascular lesions ultrasound results show only the lack of progress,without significant improvement,considering the possibility of not enough time to observate improvement in the diagnosis of ultrasound.5.Comparing the results of the 4 cases of peripheral artery atherosclerosis patients before and after treatment,the above five indicators have improved,namely the ox-LDL,TXB₂,pro-MMP-2 and MMP-2PAS were significantly below normal high-value,TIMP low than normal,and two months treatment,ox-LDL,TXB2,pro-MMP-2 and MMP-2 was significantly lower than before,while TIMP is increased.However,as to the limited sample size,we can not draw statistical conclusions suspense.Has been reduced.Experimental conclusions:1.Atherosclerosis is systemic disease,cardiovascular-medicine-doctor, should also attach great importance to patients with coronary heart disease coaliting with peripheral artery atherosclerosis at the same time concerning about coronary heart disease.2.PAS therapy is safe and effective in clinical treatment.3.PAS therapy can significantly reduce pro-MMP-2 and MMP-2 expression level of coronary heart disease patients,and effectively achieve the purpose of stabling plaque.4.PAS therapy has it's potential to reduce ox-LDL of patients with atherosclerosis,and increase the levels of TIMP and TXB₂.5.PAS therapy is proved effective to patients with peripheral artery atherosclerosis.6.PAS is expected to become a therapy of coronary heart disease, peripheral artery atherosclerosis and systemic atherosclerotic disease treatment strategy.7.limitations:If conditions permit,we can increase measurement of cytokines and inflammatory cytokines,and other related indicators to arrive at Probucol's role in the treatment of patients with coronary heart disease and corresponding treatment mechanism,for the limited experimental samples observed,time being too short,we have not yet reached the expected results, looking forward to perfecting this experiment during next phase of the experiment.