三乙酰莽草酸对凝血酶和局灶性脑缺血再灌注诱导的血小板与白细胞粘附的作用及其机制

摘要

AIM: To investigate the effect of triacetylshikimic acid (TSA)on the platelet adhesion to neutrophils and P-selectin expression on activated platelet membrane induced by thrombin and reperfusion after focal cerebral ischemia.METHODS: The platelet adhesion to neutrophils was evaluated by rosette assay,and P-selectin expression on platelet membrane was determined by flow cytometry. RESULTS: TSA 10-1000 μ mol/L markedly inhibited thrombin(0.4 kU/L)-induced platelet adhesion to neutrophils.The platelet adhesion to neutrophils induced by a 21-h reperfusion after middle cerebral artery occlusion for 3 h was also inhibited in a dosedependent manner by TSA 50-200 mg/kg given by ig immediately and at 60 min again after the onset of cerebral ischemia.TSA was also shown to decrease the P-selectin expression on platelet surface induced by thrombin in washed platelet and by adenosine dlphosphate (ADP) 5 μmol/L in whole blood.CONCLUSION:Reperfusion after cerebral ischemia and thrombin induced platelet adhesion to neutrophils,which could be reduced by TSA probably due to its inhibition of P-selectin expression on activated platelets.%目的：研究三乙酰莽草酸(TSA)对凝血酶和局灶性脑缺血再灌注诱导的血小板与中性粒细胞粘附及活化血小板膜P-选择素表达的作用.方法：观察玫瑰花环形成率作为血小板与中性粒细胞粘附率指标，并用流式细胞仪测定血小板表面P-选择素的表达.结果：TSA 10-1000 μmol/L可明显抑制凝血酶0.4kU/L诱导的血小板与中性粒细胞的粘附.TSA50-200 mg/kg剂量依赖性抑制大脑中动脉阻断3 h再灌注21 h引起的血小板与中性粒细胞的粘附.TSA可明显抑制凝血酶诱导的血小板P-选择素的表达和ADP 5 μmol/L诱导的全血中血小板膜表面P-选择素的表达.结论：脑缺血再灌注和凝血酶引起血小板和中性粒细胞粘附，TSA对P-选择素表达的影响可能是其抑制血小板与中性粒细胞粘附的重要rn机制.