ABSTRACT
Objective To observe the phosphorylation levels of extracellular signal-regulated kinase 5 (ERK5) in acute myocardial infarction (AMI) patients and the effects of ERK5 selective inhibitor XMD8-92 on human platelet activation in vitro,and to explore its mechanism.Methods Western blot was applied to detect the phosphorylation levels of ERK5,Akt473 and Akt308 in AMI patients (n =34) and stable angina patients (n =33,control).The effects of different concentration of XMD8-92 on human platelet aggregation induced by collagen was tested by aggregometer in vitro.The release of ATP was measured simultaneously by luciferase detection.The effects of XMD8-92 on integrin aIIbβ3 were detected by platelet spreading on immobilized fibrinogen and clot retraction.The effects of XMD8-92 on phosphorylation levels of Akt473,Akt308 PTEN370 and ERK5 were detected by Western blot.Results The levels of phosphor-Akt473,Akt308 and phosphor-ERK5 were significantly higher in AMI patients than that in control group (P＜0.05).ERK5 inhibitor XMD8-92 diminished collagen-induced platelet aggregation,ATP secretion,the average area of platelet spreading on immobilized fibrinogen and the clot retraction extent.The levels of phosphor-Akt (Ser-473/Thr-308) and phosphor-PTEN (Ser370) were significantly down-regulated in the presence of XMD8-92.Conclusions ERK5 plays a role in platelet activation in AMI process.It regulates platelet activation by regulating PTEN and Akt phosphorylation.Its specific inhibitor is hoped to be new antithrombotic drug.
ABSTRACT
OBJECTIVE: To study the effect of Zhenju Jiangya Tablet (ZJ) on the injured endothelial cells and endothelium-dependent relaxation function of hyperlipidemia rabbits. METHODS: Male New Zealand rabbits were randomized into four groups: control group, hyperlipidemia group, ZJ group and sivastatin group. The endothelium-dependent relaxation function was evaluated by APV using intravascular Doppler, and the morphology of endothelial cells was detected by light microscopy and electron microscopy, and nitric oxide synthase was evaluated. RESULTS: ZJ reduced the lesions of hyperlipidemia vessels, and the APV after Ach injection of each group was (1.14+/-0.26), (1.74+/-0.59), (1.22+/-0.37) and (1.17+/-0.41) respectively. The eNOS of each group was (4.21+/-0.37), (1.43+/-0.88), (3.95+/-0.67) and (4.08+/-0.46) nmol x min(-1) x g(-1) respectively. CONCLUSION: ZJ can improve the abnormality of endothelial cells and endothelium-dependent relaxation function of hyperlipidemia.
ABSTRACT
Objective To compare the effects of clopidogrel and ticlopidine in combination with aspirin in preventing direct coronary stenting complication in patients with acute myocardial infarction.Methods The clinical data of 74 cases with ST-segment elevation myocardial infarction were retrospectively analysed. The patients were divided into two groups. Before direct coronary stenting, clopidogrel,300mg loading dose then 75mg once daily or ticlopidine 250mg twice daily in addition to aspirin 100mg once daily were given to two groups respectively. Hemorrhage, neutropenia, thrombocytopenia were observed during 4 weeks. The frequency of clinical cardiovascular events (including cardiac mortality, myocardial re-infarction, need for revascularization) were followed up at 6 months. Results The incidence of major cardiac events in clopidogrel group was less than ticlopidine group ( 21.1% with Clopidogrel and 44.4% with Ticlopidine,P= 0.031). The incidence of light hemorrhage patents individually were 6(15.8%) vs 14(38.9%). The mean number of neutrophile white celll individually were 5.8 ?1.7 vs 4.2 ?3.6 (?10 9/L). The platelet count were 130.3 ?42.1 vs 89.2 ?53.3(?10 9/L), P