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In Patients With Coronary Heart Disease Platelet Activation Analysis And High-fat Rat Platelet Activation Index Evaluation And Drug Intervention

Posted on:2009-04-01Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z J WangFull Text:PDF
GTID:1114360272481839Subject:Medicine
Abstract/Summary:PDF Full Text Request
PartⅠThe study of platelet activity inpatients with coronary artery disease[objective]To evaluate the influential factors of aspirin resistance (AR),P-Selectin,11-dehydro-thromboxane B2(11-dh-TXB2),6-keto-prostag-landin F1 alpha(6-k-PGF1a) and the ratio of 11-dh-TXB2 over 6-k-PGF1a (dTP) in patients with coronary artery disease(CAD),and to estimate the relationship of the platelet activity indices with the CAD severity and with the major adverse cardiovascular events(MACE).[Method]203 patients were given one week regulationly treatment of aspirin and clopidogrel.Clinical features,blood biochemical indicators and coronary arteriography(CAG) were recorded,and the MACEs of these patients were followed up for one year.Maximum platelet agglutination rate(MPAR) induced by both ADP and AA was used to estimate AR.Enzyme linked immunosorbent assay was used to detect the serum levels of P-Selectin,TXB2 and 6-k-PGF1a,then dTP ratio was calculated.[Results]1.16 cases(7.9%) with normal CAG group were found in all 203 cases,22 cases(10.8%) for SAP group,115 cases(56.7%) for UAP group, 50 cases(24.6%) for AMI group.The diferences of AR,P-Selectin,11-dh-TXB2, 6-k-PGF1a and dTP ratio between each groups were significant and resules were showed in table 1.2.Correlative factors of platelet activity indices and the number of severe affected(CAG stenosis≥75%) coronary artery(CA) were showed in table 2.3.After one-year follow-up,55 patients(27.1%) had MACEs.P-Selectin,11-dh-TXB2,6-k-PGF1a and dTP ratio correlated to MACEs and resules were showed in table 3.4.The correlated coefficient of dTP to P-Selectin was the largest(0.766) among those indices. [Conclusion]1.The differences of AR,P-Selectin,11-dh-TXB2,6-k-PGF1a and dTP ratio in different type of CAD patients were significant.2. Diabetes,high level of hs-CRP and LDL-C were risk factors of AR.P-Selectin level,age,and hs-CRP level positively correlated to the number of severe affected CA.3.P-Selection,11-dh-TXB2,6-k-PGFla and diP ratio correlated with MACEs.4.ThedTPratiocouldreflect theplateletactivation better than other indices except for P-Selection in CAD patients.PartⅡThe evaluation of platelet activity indices and the medicinal intervention study in hyperlipidemic rats[objective]To analyze the association between various kind of platelet activation indices with the expression of CD62P on the platelet surface of hyperlipidemic rats,evaluate the change of platelet function in those rats.The effects of aspirin,atorvastatin,losartan,Fufang Danshen Diwan and Drostaglandin E1 intervention on the platelet function were also investigated. [Method]Seventy-five Wistar rats were divided into control group, hyperlipidemic group,aspirin treated group,atorvastatin treated group, losartan treated group,Fufang Danshen Diwan treated group and prostaglandin E1,treated group.After four weeks treatment,the serum levels of blood lipid were measured.HE dyeing was used for the pathological section of liver,heart and aorta.ADP and AA induced MPAR were detected and Enzyme linked immunosorbent assay was used to detect the serum levels of P-Selectin,TXB2,6-k-PGF1a.Flow cytometric analysis was applied to detect the expression of CD62P on the surface of platelet.[Results]1.After four weeks,the serum TG,TC and LDL-C in the control group compared with those in the high fat feeding group was 0.35 vs 0.88mmol/L,1.92 vs 10.72mmol/L and 0.32 vs 8.66mmol/L respectively.2.The correlated coefficient of P-Selectin to CD62P was the largest(0.847) among all indices.3.After four weeks drug intervention,the levels of ADP and AA induced MPAR,TXB2,6-k-PGF1a,TP ratio,P-Selectin and CD62P in each group were significantly different and results were showed in table 1.[Conclusion]1.P-Selectin level could reflect the platelet activation better than than other indices except for CD62P in Wistar rats.2. Hyperlipidemia could increase platelet activation which could be significantly inhibited by aspirin.3.Atorvastatin can not only regulate dyslipidemia but also inhibit platelet activation remarkably.4.Losartan, Fufang Danshen Diwan and prostaglandin E1 could inhibit platelet activation to some extend.
Keywords/Search Tags:coronary heart disease, AR, platelet activation, MACE, hyperlipemia, P-Selectin, CD62P, drug intervention
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