Effect of Resveratrol on Preventing Steroid-induced Osteonecrosis in a Rabbit Model

摘要

Background:Prevention of osteonecrosis (ON) has seldom been addressed.The purpose of this study was to evaluate the effect of resveratrol on preventing steroid-induced ON in rabbits.Methods:Seventy-two rabbits were divided into four groups:(1) NEC (ON) group:thirty rabbits were treated with lipopolysaccharide (LPS) once,then with methylprednisolone (MPS) daily for 3 days;(2) PRE (prevention) group:thirty rabbits were given one dose of LPS,then MPS daily for 3 days,and resveratrol on day 0 and daily for 2 weeks;(3) RES (resveratrol) group:six rabbits were given resveratrol for 2 weeks but without LPS/MPS;(4) CON (control) group:six rabbits were given alcohol for 2 weeks but without LPS/MPS.Levels of plasma tissue-type plasminogen activator (t-PA),plasminogen activator inhibitor 1 (PAI-1),thrombomodulin (TM),vascular endothelial growth factor (VEGF),maximum enhancement (ME) by magnetic resonance imaging,and ON incidence were evaluated.Results:The PRE group had a lower ON incidence than the NEC group,but with no significant differences at 2 weeks and 12 weeks.The RES and CON groups did not develop ON.TM and VEGF were significantly higher in the NEC group compared with the PRE group at weeks 1,2,and 4 (TM:1 week,P =0.029;2 weeks,P =0.005;and 4 weeks,P =0.047;VEGF:1 week,P =0.039;2 weeks,P =0.021;4 weeks,P =0.014),but the difference disappeared at 12 weeks.The levels of t-PA and PAl-1 were not significantly different between the NEC and PRE groups.The TM,t-PA,PAI-l,and VEGF concentrations in the RES and CON groups did not change over time.Compared to the baseline,ME in the NEC group decreased significantly (P =0.025) at week 1,increased significantly (P =0.021) at week 2,and was decreased at week 12.The variance was insignificant in the PRE group.Conclusions:Resveratrol may improve blood supply to bone in a rabbit model of ON of the femoral head via anti-inflammatory effects to protect the vascular endothelium and reduce thrombosis.