Membrane Particles And Rabbit Femoral Head Ischemic Necrosis Of The Experimental Study Of Mechanism Of Drug Intervention

Objective:To investigate the alterations of endothelial- and platelet-derived microparticles and the change of coagulation and inflammation in the steroid-induced avascular osteonecrosis of femoral head with/without an intervention agent.Method:Twenty-seven healthy New Zealand rabbits were included and randomized into 3 group:Group A(the control group,n=9) would be injected once intramuscularly with the same dose of 0.9%NaCl solution as the steroid group;Group B(the steroid group,n=10) would be injected once intramuscularly with 20 mg/kg of methylprednisolone;Group C(the intervention group,n=8) would receive a intervention agent continuously for 12 days and a injection of 20 mg/kg methylprednisolone once intramuscularly on the day 7 of intervention.The blood sample should be collected before injection of methylprednisolone and day 1,day 3, day 7,day 14 and day 28 after the injection.The microparticles expressing CD31+/CD42b-and CD31+/CD42b+ would be measured using flow cytometry.And the antithrombin-Ⅲ(AT-Ⅲ),protein C(PC) and fibrinogen(FIB) were also examined. Tumor necrosis factor alpfa(TNF-α) and interleukin 1 beta(IL-1β) would be measured using Array-ELISA.Three rabbits from the steroid group were sacrificed and their femoral heads were taken out to undergo histopathologic examination with HE staining in 4 weeks after the injection.Results:The AT-Ⅲ,PC levels decreased significantly 7 to 28 days and the FIB level increased on day 7 without significance and then decreased slightly after the injection. The numbers of EMP and PMP were also increased markedly after steroid administration.Both TNF-αand IL-1βlevels increased relative to the baseline, and were greater than the control group at each time point,but no significance was observed.No positive finding was observed in the histopathologic examination.Conclusion:High-dose glucocorticosteroid increases the levels of PMP and EMP that may be related to hypercoagulability,thrombosis and inflammation in microcirculation and play an important role in steroid-induced osteonecrosis.The intervention agent appeared to have the efficacy to decrease the MP levels and improve the hypercoagulability and thrombosis.MP can be considered a true target in the pharmacological control of steroid-induced osteonecrosis.