【作者】 李挺松；

【导师】 肖增明；

【作者基本信息】 广西医科大学 ， 骨科学， 2004， 硕士

【摘要】 目的：采用激素（地塞米松，Dexamethasone）制作成兔股骨头坏死(Steroid-induced Femoral Head Necrosis, SIFHN) 模型，探讨普拉固（Pravastatin）对SIFHN干预作用及其机制。方法：12-18周龄日本大白兔42只，雌雄不限，体重2.50.6kg,随机分为4组：空白组（Group A）：6只。对照组(单纯激素组Group B)：12只。小剂量普拉固组（Group C）：12只，普拉固口服5mg/天。大剂量普拉固组（Group D）：12只，普拉固口服10mg/天，各组动物均以标准饲料及草料喂养，除A组外，B,C,D组均以Dexamethasone 2.5mg/kg·d im，用足12周。期间每组均予青霉素80万u/只， im。链霉素1.0g/只，im，2次/周，防止感染。分别于6周，8周，10周，12周处死每组兔子各3只，处死前均检查血脂，血粘度，血PT,t-PA及双髋关节x-ray摄片，处死后取双股骨头行HE染色，标本行光学电镜观察，及透射电镜检查，细胞凋亡分析。结果: 普拉固组中小剂量组及大剂量组的兔血脂，血粘度 PT, t-PA较激素组均升高 （P<005）。与单纯激素组比较，普拉固组X-ray 示股骨头及髋臼可见软骨下区不规则囊性透亮区及骨化硬化带明显减少，HE染色示骨小梁未见稀疏，骨陷窝空虚率，髓内基质细胞脂肪转化率减低，髓内血管栓子形成减少。透射电镜示骨细胞吞饮脂滴减少。细胞凋亡分析示实验组较对照组骨细胞凋亡指数减少（P<005）。但普拉固这种对SIFHN的干预作用，大小(10mg/d与5mg/d)剂量间不存在显著差异。结论: 地塞米松能在兔体内成功造成股骨头坏死模型，而他汀类药物普拉固能有效干预股骨头坏死进展，其作用机制可能与降血脂，血粘度，抗凝，从而缓解股骨头血供障碍，减少骨质疏松避免软骨下骨骨折，降低骨内压有关。更多还原

【Abstract】 Object : To build a model of rabbits’ Steroid-induced Femoral Head Necrosis (SIFHN) by administing Dexamethasone(DEX). Discussing whether the Provastatine can intervening the course of resulting in SIFHN and the possible mechanism. Methods: The Japanese rabbits, 12-18 weeks old ,2.50.6kg, randomly divided into 4 groups, Group A(n=8): Just used as the control. Group B(purely administering DEX n=12).Group C(n=12): Pravastatin 5mg/d p.o. Group D(n=12): Pravastatin 10mg·d-1 p.o. Every rabbit of group A B C was fed by standard forage and fodder. DEX of 2.5mg·kg-1·d-1 was injeceted to the rabbits except Group A for 12 weeks. Simultaneity, the Penicillin-natrium 80,0000u and streptomycin 1.0g was injected to everyone ,twice a week, avoiding being infected. Every following 6,8,10,12 weeks, 3 rabbits of every group were selected to examined with serum cholesterol and triglyceride, hemorrhelogical factor, PT, tissue plasminogen( t-PA) and double hipcoxa joints were taken an X-ray photograph before they were executed . The specimens of double femoral heads were taken to studied by the light microscope after stained with Hematoxylin and eosin(HE), Transmission Electron Microscope(TEM) and analyse of apoptosis. Result: Comparing with the Group B, the serum cholesterol and triglyceride, hemorrhelogical factor levels of the Group C and D had lowered obviously, PT and t-PA are higher since 6 weeks (P<0.05),X-ray didn’t show the phenomenons of the irregular radiolucent cystic area and ossificational cirrhosis that was found clearly in the subchondral region of the acetabulum and femoral head. Light microscopy exhibit the density of trabecular bone did not change more than Group A. The rate of the empty lacuna and the bone marrow stromal cell transforming to the lipocyte had decreased obviously . There is seldom fat embolus and lipid droplets appearing in the vessels of the osteocytes. Under the TEM, organelle and nucleus of osteocytes were found rarely degenerative, necrotic and swallowing the lipid droplets. The analyse of apoptosis present the AI(Apoptosis Index) was lower than Group B（P<005） .The effect of <WP=5>Pravastatin intervening the course of SIFHN did not show markedly difference between the Group C and D. Conclusion: The Dexamethasone resulted in building the model of rabbits’ SIFHN as the Group B. and the Pravastatin can intervene the couse of SIFHN effectively .The mechanism of action is mightly related with lowering the level of serum lipid and hemorrhelogical factor, releasing the osteoporosis, which would reduce the obstructive possibility of blood supply and the rate of fracture that happened below the subchondral region of femoral head.更多还原