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单次低剂量脂多糖联合甲基强的松龙诱导股骨头坏死的实验研究
引用本文:杨建平,王黎明,徐燕,樊克武,王劲松.单次低剂量脂多糖联合甲基强的松龙诱导股骨头坏死的实验研究[J].中国修复重建外科杂志,2008,22(3):271-275.
作者姓名:杨建平  王黎明  徐燕  樊克武  王劲松
作者单位:1. 南京医科大学附属南京第一医院骨科,南京,210006
2. 南京医科大学附属南京第一医院病理科,南京,210006
摘    要:目的 探讨单一低剂量脂多糖(lipopolysaccharide,LPS)及后续3次高剂量甲基强的松龙(methylprednisolone,MPS)注射引起激素性股骨头坏死(osteonecrosis of femoral head,ONFH)的发生情况及其发生机制. 方法 健康成年雄性26~30周龄新西兰大白兔25只,体重(3.0 ±0.3)kg.随机取19只为处理组,经耳缘静脉注射10 μg/kg LPS,24 h后于右侧臀肌注射20 mg/kg MPS琥珀酸钠,共3次,每次间隔24 h;余6只为对照组,于相同时间点注射等量生理盐水.于注射LPS前、3次注射MPS前及最后1次注射MPS后24 h行血液学检查.于最后1次注射MPS后6周行双髋部MRI扫描,于股骨头区抽吸骨髓检测局部干细胞活性,并取双侧股骨头行组织病理学检查. 结果 LPS注射后48 h,1只动物死亡,余动物均存活至实验完成.经组织病理学观察,处理组中16只动物为ONFH (病理),ONFH发生率为88.9%(16/18),坏死区域主要位于干骺端,微血管内有纤维血栓形成,髓内脂肪细胞体积明显增大并堆积;对照组股骨头均正常.MRJ诊断准确率为93.8%(15/16).处理组中16只ONFH (病理)动物,与正常值(注射LPS前)比较组织纤溶酶原激活剂/纤溶酶原激活剂抑制因子1(tisssue plasminogen aetivator/plasminogen activator inhibitor 1,t-PA/PAI-1)和活化部分凝血激酶时间(activated partial thromboplastin time,APTT)明显下降(P<0.05),低密度脂蛋白/高密度脂蛋白明显增高(P<0.05);对照组以上指标与正常值比较差异均无统计学意义(P>0.05).各时间点处理组ONFH (病理)动物t-PA/PAI-1和APTT与对照组比较,差异有统计学意义(P<0.05).处理组ONFH (病理)兔股骨头区骨髓产生的成纤维细胞集落形成单位总数为8.50 4±9.63,与对照组的70.17±7.78比较,差异有统计学意义(P<0.05). 结论 单次低剂量LPS联合MPS是制备激素性ONFH模型的成功方法,血液的高凝和/或高纤溶状态、脂质代谢的紊乱、多能干细胞数量活性的降低等多因素作用可能是诱导激素性ONFH的关键.

关 键 词:激素性股骨头坏死  发生机制  早期诊断  模型制备    低剂量  糖联  甲基强的松龙  股骨头坏死  实验  研究  LIPOPOLYSACCHARIDE  SINGLE  COMBINATION  INDUCED  OSTEONECROSIS  OF  FEMORAL  HEAD  作用  因素  活性  细胞数量  脂质代谢  纤溶状态  血液  模型  集落形成单位
收稿时间:2007-08-29
修稿时间:2007-12-06

AN EXPERIMENTAL OSTEONECROSIS OF FEMORAL HEAD INDUCED BY A COMBINATION OF A SINGLE LOW-DOSE LIPOPOLYSACCHARIDE AND METHYLPREDNISONE
YANG Jianping,WANG Liming,XU Yan,FAN Kewu,WANG Jinsong.AN EXPERIMENTAL OSTEONECROSIS OF FEMORAL HEAD INDUCED BY A COMBINATION OF A SINGLE LOW-DOSE LIPOPOLYSACCHARIDE AND METHYLPREDNISONE[J].Chinese Journal of Reparative and Reconstructive Surgery,2008,22(3):271-275.
Authors:YANG Jianping  WANG Liming  XU Yan  FAN Kewu  WANG Jinsong
Institution:Department of Orthopeadics, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing Jiangsu, 210006, P. R.China.
Abstract:OBJECTIVE: To investigate both incidence and mechanism attributing to steroid-associated osteonecrosis of femoral head (ONFH) using an experimental protocol with a single low-dose lipopolysaccharide (LPS) injection and subsequently three injections of high-dose methylprednisolone (MPS). METHODS: Twenty-five New Zealand white rabbits with body weight of (3.0 +/- 0.3) kg were divided randomly into 2 groups. In treatment group, 19 rabbits received one intravenous injection of LPS (10 microg/kg); 24 hours later, three injections of 20 mg/kg of MPS were given intramuscularly at an interval of 24 hours. Additional 6 rabbits which received normal saline injection at the same time point were used as controls (control group). The blood samples were collected for hematological examinations before and after LPS injection, MRI was performed on bilateral hip six weeks after last MPS injection, meanwhile, bone marrow was aspirated from femoral head region to evaluate stem cell's activity. Bilateral femoral heads were harvested to make histopathology examination. RESULTS: All animals survived throughout the experiment period except one death on the second day after LPS injection. In the histopathological examination for the femoral head, ONFH+ was observed in 16 rabbits (88.9%), and the lesions were mainly in the metaphysis. In ONFH+ rabbits, micro vessels fibrous thrombosis and extravascular marrow fat cell size increasing were found around necrotic bone; The femoral heads of control group had no changes. MRI accurate ratio was 93.8% (15/16). Compared to baseline, a significant decrease in ratio of tissue plasminogen activator/plasminogen activator inhibitor 1 and activated partial thromboplatin time, and a significant increase in ratio of low-density lipoprotein/high-density lipoprotein were only found in ONFH+ rabbits (P < 0.05). Meanwhile there was a significant decrease in the number of CFU-F (8.50 +/-9.63) compared with the control (70.17 +/- 7.78, P < 0.05). CONCLUSION: A single low-dose LPS injection and subsequent three injections of high-dose MPS is effective on building steroid-associated ONFH model, coagulation and lipometabolism abnormality, activity degeneration of stem cell may be the key factors of ONFH.
Keywords:Steroid-associated osteonecrosis of femoral head Pathogenic mechanism Early diagnosis Model building Rabbit
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