The effects of dual antiplatelet on platelet function in sepsis rats and acute lung injury

doi:10.3969/j.issn.1002-1949.2015.02.001

Abstract：Objective The present study aims to investigate the effect of aspirin and dual antiplatelet on platelet function in sepsis rats and acute lung injury.Methods Forty male Wistar rats were randomly divided into five groups (n=8 each): control group (N), endotoxin group (LPS), aspirin group ( A) , clopidogrel group ( C) , aspirin plus clopidogrel group ( A+C) .The rats in N and LPS group were respectively treated with normal saline 1 mL while A, C and A +C group were respectively given aspirin (100 mg/kg), clopidogrel (200 mg/kg), aspirin (100 mg/kg)+clopidogrel (200 mg/kg) pretreatment by gavage for three days.Then, rats in tested groups were administered with LPS (10 mg/kg) through the intraperitoneal.Six hours after modeling, the histopathology of the lung was observed by light microscope, lung wet/dry weight ratio and PaO2 were measured, PaO2/FiO2 was calculated, the expression level of platelet CD62P and TLR4 were measured by flow cytometry instrument, the concentration of TNF -αand IL -6 in serum were observed by ELISA, the rate of platelet aggregation was assayed by impedance platelet aggregometry.Results The level of PaO2 , PaO2 /FiO2 decreased while the rate of platelet aggregation, the expression of platelet CD62P and TLR4, lung WD/ratio, the concentration of TNF -αand IL-6 were significantly increased in LPS group compared with N group (P<0 .01).Platelet aggregation, the expression level of platelet CD62P and TLR4, lung W/D ratio, the concentration of TNF-αand IL -6 were significantly lower in intervention groups than those in LPS group, PaO2, PaO2/FiO2 were improved (all P<0.05), the most obvious change occurred in dual antiplatelet group among intervention groups (P<0.01).Compared with N group, infiltration of inflammatory cell,interval widened , deformation and fracture of alveolar were found in LPS group, and treatment A or C or A+C could relieve lung injury.Concluis on LPS-induced ALI could be significantly alleviated by the dual antiplatelet of combination of aspirin and clopidogrel. Down-regulating of the expression of TNF-α, IL-6 and inhibiting the excessive of platelet activation and aggregation maybe the mechanism.