非创伤性骨坏死血栓前状态的实验研究

A preliminary study of the prethrombotic status of the blood in animal models of nontraumatic osteonecrosis

目的探讨实验性非创伤性骨坏死血栓前状态的发病机制。方法16只成年家兔随机分为两组 ,单纯内毒素组8只 (A组 ) ,间隔24h于耳缘静脉注射大肠杆菌内毒素 (lipopolysaccharide,LPS) ,共2次 ,每次50μg/kg;内毒素 +激素组8只 (B组 ) ,内毒素注射方法同A组 ,并于第二次注射内毒素24h后肌内注射甲基强的松龙20mg/(kg·d),连续注射3d ,制备典型的骨坏死动物模型。在用药前后不同时间行心内穿刺抽取血标本 ,用放射免疫法测定血栓素B2 (TXB2)、6 -酮 -前列腺素F1αHL(6 -Keto -PGF1α)、血小板α -颗粒膜蛋白 (GMP -140)和血栓调节蛋白 (TM )的血浆含量 ;用发色底物法测定组织型纤溶酶原活化物 (t -PA)和纤溶酶原活化物抑制物 (PAI)的纤溶活性。结果第二次应用内毒素后12h和24h ,血浆TXB2、6 -Keto -PGF1α、GMP -140和TM均升高 ,但以12h升高最为明显 (P<0.05)。应用激素3d后的24h ,B组TXB2、6 -Keto -PGF1α 升高 ,但与A组比较差异无显著性意义 (P>0.05)。第二次应用内毒素后12h ,两组血浆t -PA含量下降 ,PAI升高,与其他各时限比较差异有显著性意义 (P<0.05)。应用激素3d后24h ,B组t-PA下降 ,PAI升高 ,与A组比较差异有显著性意义 (P<0.05)。结论内毒素与激素均有促进血液高凝和纤溶活性下降的作用 ,二者联合毒?

Objective To study pathogenesis of the prethrombotic status of the blood in experimental nontraumatic osteonecrosis. Methods 16 rabbits were divided randomly into 2 groups: Group A of lipopolysaccharide (LPS ) , 8 rabbits received 2 doses of 50 μg/kg of LPS intravenously at an interval of 24 hours, Group B of combined LPS with steroid, 8 rabbits received 2 doses of 50 μg/kg of LPS as in Group A and 24 hours later was given 20 mg/(kg·d) of methylprednisolone acetate intramuscularly for 3 days after the second injection of LPS. Blood samples were collected from heart puncture immediately before and at various times after the injection. TXB2,6-Keto-PGF1α,GMP-140,TM were examined with RIA. t-PA and PAI were examined with chromogenic assay. Results 12th hour and 24th hour after the 2nd injection of LPS,TXB2, 6-Keto-PGF1α,GMP-140 and TM increased,however, 12th hour after the injection, the increase were more remarkable (P< 0.05). 24th hour after the injection of prednisolone acetate for 3 days, TXB2 and 6-Keto-PGF1αincreased in comparison with that in Group A, however, there is no significance difference between them (P >0.050). 12th hour after the 2nd injection of LPS, t-PA drops and PAI augmented. There was significant difference between Group A and Group B(P< 0.05). 24th hour after the injection of prednisolone acetate for 3 days, t-PA drops and PAI increased in comparison with that of Group A, and their difference was significant (P< 0.05). Conclusion Both LPS and steroid can induce hypercoagulable and hypofibrinolytic status and the combined effect can exhibit even stronger toxicity. Apparently they are important inducing factors of nontraumatic osteonecrosis.