甲基强的松龙联合内毒素诱导兔股骨头缺血性坏死的实验研究  

EXPERIMENTAL STUDY ON AVASCULAR NECROSIS OF FEMORAL HEAD INDUCED BY METHYLPREDNISOLONE COMBINED WITH LIPOPOLYSACCHARIDE IN RABBITS

作　　者：马焕芝[1] 曾炳芳[1] 李晓林[1] 柴益民[1] 

机构地区：[1]上海交通大学附属第六人民医院骨科,上海200233

出　　处：《中国修复重建外科杂志》2008年第3期265-270,共6页Chinese Journal of Reparative and Reconstructive Surgery

基　　金：国家自然科学基金资助项目(30571898)~~

摘　　要：目的建立兔激素性股骨头缺血性坏死模型,为进一步研究早期股骨头缺血性坏死的治疗奠定基础。方法健康成年雄性新西兰白兔36只,体重3～4kg,根据给药方式不同随机分成4组。A组(n=10):于耳缘静脉注射大肠杆菌内毒素(10μg/kg),24h后重复给药1次;B组(n=10):大肠杆菌内毒素注射同A组,注射完毕后,立即臀肌注射甲基强的松龙(40mg/kg)3次,每次间隔24h;C组(n=10):单纯臀肌注射甲基强的松龙(40mg/kg)3次,每次间隔24h;D组(n=6):与B组相同时间点注射等量生理盐水,作为对照。注射后观察动物一般情况;于注射前及末次注射后2、4及6周,行MRI检查,观察股骨头改变;6周时通过组织学检查、墨汁血管灌注和透射电镜观察各组股骨头病理和血管形态变化,并计算空骨陷窝率、微血管密度和骨小梁面积百分比,根据组织学和MRI检查结果计算各组骨坏死发生率。结果A、B组动物注射内毒素后出现精神萎靡,眼睑充血发红等症状,活++动及饮食减少。B、C组动物于末次注射后3周明显消瘦,体重减轻;A、D组动物于末次注射后4周体重增加。B、C组分别于末次注射后2d和16d各有1只动物死亡。注射前及末次注射后2周各组动物股骨头MRI信号未见异常。4、6周时B、C组股骨头MRI检查T1WI表现为不规则低信号,T2WI呈高信号或低信号;A、D组股骨头MRI信号未见异常。A、B、C及D组空骨陷窝率分别为11.8%±4.7%、34.4%±6.2%、20.0%±4.7%、9.3%±4.6%;骨小梁面积百分比分别为59.2%±6.8%、40.1%±6.0%、51.5%±5.6%、63.2%±8.3%;微血管密度分别为14.3%±2.7%、4.5%±2.1%、10.2%±3.1%、15.4%±4.1%;各指标B组与A、C及D组比较,差异均有统计学意义(P<0.01)。透射电镜观察,B组和C组骨细胞和内皮细胞胞浆内均出现脂滴,B组骨细胞皱缩,核膜失去连续性、染色质溶解或固缩,A组和B组血管内皮细胞肿胀,细胞之间的连接增宽、破坏。B组骨坏死发生率为88.9%,显著Objective To establish a stable animal model for glucocorticoid-induced avascular necrosis of femoral head in rabbits. Methods Thirty-six adult New Zealand rabbits were randomly divided into four groups： ten were injected twice with lipopolysaccharide （group A）, ten were treated with a combination of lipopolysaccharide and methylprednisolone （group B）, ten were injected three times with methylprednisolone （group C）, and six were injected normal saline as a control （group D）. MR imaging was performed in the rabbits before the first injection of lipopolysaccharide or methylprednisolone, and at 2, 4, and 6 weeks after the last injection of lipopolysaccharide or methylprednisolone. Histopathological changes in the femoral heads were observed by light microscope and transmission electron microscope at the end of six weeks after the injection. Vascular infusion with Chinese ink was made to evaluate the morphological changes of blood vessels in the femoral head. The percentage of trabecular bone area and empty lacunae and microvascular density were measured. According to the histological and MR imaging appearance of the femoral heads in all groups, the incidence of osteonecrosis of every group was calculated. Results Listlessness, blepharal hyperemia, less activity and reduced diet were found in the rabbits of groups A and B after injected withlipopolysaccharide. At 3 weeks after the final injection, the body weight of groups B and C was decreased. At 4 weeks after the final injection, the body weight of groups A and D was increased. No abnormal signal could be detected on MR images in rabbits of all groups before injection and at 2 weeks after the injection. At 4 weeks and 6 weeks after the last injection, irregular low signal on T1- weighted images and irregular low or highsignal on T2-weighted images could be detected on MR images in rabbits of groups B and C, no abnormal signal could be detected on MR images in rabbits of groups A and D. At 6 weeks after the last injection, the trabecular bone of g

关 键 词：股骨头缺血性坏死 甲基强的松龙 内毒素 动物模型 兔 

分 类 号：R681.8[医药卫生—骨科学] R629.28[医药卫生—外科学]