| Objective:Platelet adhesion an aggression play a crucial role in the the formation of thrombus baced on aherosclerosis(AS). The interaction between the platelet receptor glycoprotein(GP)Ib-IX-V complex and von Willebrand factor(VWF) plays a key role in initiation of platelet adhesion and arterial thrombus formation at the sites of vascular injury,and it’s also plays a important role in the pathogenesis of platelet adhesion and aggregation under high shear stress conditions at the site of pathological hemadostenosis.Therefore,GPIb has long been suggested as a desirable antithrombotic target.Agkisacuctin,a protein isolated from snake venom, is a new inhibitor of platelet,who can prevent the formation of thrombus by inhibiting the GPIb-v WF interaction and subsequently platelet adhesion or aggregation.The purpose of this paper is: Firstly,to explore the effect of glycoprotein(GP)Ib antagonist Agkisacuctin on platelet aggression induced by different agonist.To study the effect on platelet aggression in human.Secondly,to explore the effect of glycoprotein(GP)Ib antagonist Agkisacuctin on platelet CD62 p expression. To study the effect of Agkisacucetin on platelet release reaction.This study could provide a reference for the early clinical trials.Methods: This study includs 50 health volunteers from Hospital Madical Center during March to June.Early in the morning, drawing blood of elbow vein on an empty stomach, to the platelet-rich plasma(PRP) separation.The exiperiment consists of two parts.The first test is to explore the effects of Agkisacucetin on platelet agrression.Firstly,the maximal platelet aggregation(r PA,max) induced by adenosine diphosphate(ADP,final concentration 5μmol/L) or Ristocetin(final concentration final60mg/m L)(follow were same)which were both as the control group were detectded.Secondly,Agkisacucetin with different concentrations(0.5、1.0、2.0、4. 0、8.0μg/ml,follow were same)intervent separately the platelet aggression induced by Ristocetin or ADP,which were as the trial group,the r PA,max of them were detected. Then the differences between the tial group and the control group were discussed.The correlations between the different concentrations of Agkisacucetin and the inhibition rate of platelet r PA,max by Agkisacucetin were explored.This experiment was operated on platelet aggregation instrument.The second test which were divided into three group experiment was to explore the effects of Agkisacucetin on platelet CD62 p expression.The first group,was to detect platelet CD62 p expression in resting state which was as the blank group,induced by ADP or Ristocetin which was as the trial goup,to explore the difference between the tial group and conrol group,and the difference of the two trial group.The second group,the platelet CD62 p expression in rest state was as the blank control group,and induced by ADP was as the positive control group,to detect platelet CD62 p expression induced by Agkisacucetin which was as the trial groups.to explore the difference between the trial groups and the blank control group,and the difference of trials.The correlations between the different concentrations of Agkisacucetin and the platelet CD62 p expressi induced by Agkisacucetin were explored. The third group,the platelet CD62 p expression induced by ADP was as the positive control group,Agkisacucetin with different concentrations intervent separately the platelet CD62 p express induced by ADP,which were as trials group.The difference between the trials group and the positive group and the correlations between the inhibiton rate and concentrations of Agkisacucetin were detected.Results:1.The platelet r PA,max induced by Ristocetin was 85.26±8.25%.Comparing to control group,the platelet r PA,max induced by Ristocetin which under the interventions of Agkisacucetins with different concentration were lower than control group.The differences all were statistically significant(P<0.05).The inhibitons rate ofAgkisacucetin for the r PA,max were increased as the increases of concentrations.They were positive correlation(r=0.936,P<0.05).The concetration for 50% maximal effect(EC50) was about 2.0μg/m L.2.The platelet r PA,max induced by ADP was 85.26±8.25%.Comparing to control group,the platelet r PA,max induced by ADP which under the interventions of Agkisacucetins with different concentrations were not significant difference(P>0.05).The maximal inhibition rate were 3.05±0.39%.3.The platelet CD62 p expression in the control group was 6. 56±2.91%.and in trial group which induced by Ristocetin was 10.81±4.5 0%,that had no significantly difference between them(P>0.05).The CD62 p expression intrial group which induced by ADP was 68. 82±6.02%,which was much higher than the control group,they were significantly different(P<0.05).The trial group which induced by Ristocetin was much lower than the trial group which induced by ADP.,the difference between them were statistically significant(P<0.05).4.The platelet CD62 p expression in the trial groups which induced by the different concentrations of Agkisacucetin were all little higher than the blank control group which was in rest state.but the difference between them wasn’t statistically significant(P>0.05),comparing to positive control group which induced by ADP was much lower,and the difference between them was statistically significant(P<0.05). 5.The trial group which was the intervention of Agkisacucetin with different concentrations for platelet CD62 p expression induced by ADP was little higher than the positive control group induced by ADP. The difference between them wasn’t statistically significant(P>0.05),The maximal in trial groups was 72.13±5.26%,the difference between it and the positive was 3.25±1.02%,and they weren’t statistically significant(P>0.05).Conclusion:Agkisacucetin could inhibit r PA,max indued by Ristocetin significantly.The effect of Agkisacucetin on r PA,max had positive correlation with the concentrations.Agkisacucetin had no effect on r PA,max induced by ADP.Agkisacucetin had no effect on platelet CD62 p expression,and could not inhibit platelet CD62 p expression.Agkisacucetin could not inhibit the platelet CD62 p expression,and itself had little effect on the platelet CD62 p expression.Agkisacucetin had little effect on platelet release reaction compared to effect on platelet aggression. |
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