The Function Of Dexamethasone And Methylprednisolone On Platelet Aggregation

Objective:Craniocerebral injury activate hematopoietic system and induce hypercoagulable states,hypercoagulability and subsequent Hyperfibrinolysis can cause cerebral hemorrhage and disseminated intravascular coagulation(DIC)which can produce severe influence on the prognosis of injury.Glucocorticoid,such as dexamethasone(DXM)and methylprednisolone are widely used in clinication.High dose dexamethasone maybe advance activation of blood platelets,however methylprednisolone inhibit ADP which can cause platelets aggregation and liberation. We also noticed converse reports.Comparative study of DXM and methylprednisolone on platelet aggregation in vivo and in vitro cannot be found.Our purposes are:1^st,by the experiment of human in vitro,compare various effects on blood platelets packing fraction under the different action time on platelet-rich plasma (PRP),different inducer concentration of DXM and methylprednisolone;2^nd,by the experiment of Wister rats in vivo,verticate results of human in vitro tests and investigate mechanism of two drugs on blood platelets packing fraction furtherly.It can rise leading meaning on the clinical treatment,and provide new ideas on the exploitation of new drugs.Methods:1 The experiment of human in vitro,get blood from healthy male volunteer by ulnar vein,prepare abundant platelet-rich plasma(PRP)platelet-poor plasma(PPP).Different doses DXM and methylprednisolone were added in PRP of experimental groups,equivalence physiological saline were added in PRP of control group;they were put in the thermostat container simultaneously.At 30 minutes,60 minutes,90minutes,PRP including DXM or methylprednisolone,and adopted inducer of 1μM及5μM ADP,and determine blood platelets packing fraction by turbidimetry.2 The experiment of Wister rats in vivo:healthy male Wister rats,eight rats in large dose DXM group,low DXM group,large dose methylprednisolone group,low dose methylprednisolone group respectively.Blood obtained from vena orbitalis anterior before administration were tested by turbidimetry,which were regarded as control before administration.DXM and methylprednisolone were injected from caudal vein;1 hour later,blood obtained from vena orbitalis anterior were tested by turbidimetry under the inducer of 5μM ADR 3 Statistical analysis, compare the influences and clinical significance of DXM and methylprednisolone on blood platelets packing fraction.Results:1.Human DXM experiment in vitro,supramaximal dose of DXM (2mg/kg,concentration of ADP was 5μM)facilitate blood platelets aggregation significantly;large dose of DXM(0.3mg/kg,concentration of ADP inducer was 1μM and 5μM)facilitated blood platelets aggregation significantly;low dose of DXM (0.08mg/kg,concentration of ADP inducer was 1μM and 5μM)showed no action.2. Human methylprednisolone experiment in vitro,supramaximal dose of methylprednisolone(15mg/kg,concentration of ADP inducer was 1μM and 5μM) inhibited blood platelets aggregation significantly;low dose of methylprednisolone (0.6mg/kg,concentration of ADP inducer was 1μM)did not inhibit blood platelets aggregation significantly;low dose of methylprednisolone(0.6mg/kg,concentration of ADP inducer was 5μM)inhibit blood platelets aggregation significantly.3.Wister rats DXM experiment in vivo,large dose of DXM(1.9mg/kg,concentration of ADP inducer was 5μM)facilitated blood platelets aggregation significantly;low dose of DXM(0.5mg/kg,concentration of ADP inducer was 5μM)appeared no obvious effect on blood platelets aggregation.4.Wister rats methylprednisolone experiment in vivo,high dose of methylprednisolone(94mg/kg,concentration of ADP inducer was 5μM)facilitated blood platelets aggregation significantly;low dose of DXM (3.75mg/kg,concentration of ADP inducer was 5μM)appeared no obvious effect on blood platelets aggregation.Conclusions:1.In the experiment of human in vitro,large dose of DXM prompted blood platelets aggregation;large dose of methylprednisolone inhibited blood platelets aggregation;low dose of DXM and methylprednisolone showed no obvious effects on blood platelets aggregation.2.In the experiment of Wister rats in vivo,large dose of DXM prompted blood platelets aggregation;large dose of methylprednisolone inhibited blood platelets aggregation;low dose of DXM and methylprednisolone showed no obvious effects on blood platelets aggregation.3.By turbidimetry,we can test blood platelets aggregation and detect DXM and methylprednisolone's effect on blood platelets aggregation,optimal time window was 60 minutes.Measurement of blood platelets aggregation should be completed in 2.5 hours after intravenous blood collection.4.Detection degree of aggregation of blood platelets and drugs' effects on them by means of ADP inducer;when concentration of ADP inducer was 5μM,it can reflect drug effects on blood platelets aggregation susceptiblely.5.Converse effects on blood platelets aggregation of DXM and methylprednisolone were showed in human vitro and Wister rat vivo tests,concrete mechanism of action must be studied furtherly.DXM and methylprednisolone were widely applied in clinical domains,it can rise leading meaning on the clinical treatment,and provide new ideas on the exploitation of new drugs.