普拉固对兔激素性股骨头坏死骨细胞凋亡的干预研究

A STUDY OF EXPERIMENTAL RABBITS FOR INTERVENING THE APOPTOSIS OF OSTEO CYTES IN THE COURES OF STEROID-INDUCED FEMORAL HEAD NECROSIS(SIFHN) BY PRAVA STATIN

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）是否能干预SIFHN中骨细胞凋亡。方法：12～18周龄日本大白兔34只，雌雄不限，体重（2．5±0．6）kg，随机分为3组：对照组（A组）：6只，单纯标准饲料及草料喂养。实验组（B组）：14只，Dexamethasone 2．5mg／kg·d。肌注。干预组（C组）：14只，Dexamethasone2．5mg／kg·d^-1肌注＋普拉固2．5mg／kg·d^-1口服。期间每组均予青霉素80万单位／只，肌注，链霉素1．0g／只，肌注，2次／周，防止感染。分别于6、8、10、12周处死每组兔子各3只，实验开始及处死前均检查血脂、血Prothrombin Time（PT）、tissueplasminogen（t-PA），处死后行光镜下细胞凋亡分析。结果：C组的兔血脂较B均降低（P〈0.05），PT较实验组均降低（P〈0．05），t—PA较B组升高（P〈0．01）。与B组比较，光镜示细胞凋亡分析指数减少（P〈0．01）。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SIFHN中骨细胞凋亡，其作用机制可能与降脂、抗凝、调控凋亡基因表达等因素有关。

Objective：To set up a model of rabbits＇ Steroid-induced Femoral Head Necrosis （SIFHN） by administering Dexamethasone（DEX）, and to discuss whether Pravastatin can interven the apoptosis of osteo- cytes in the course of Steroid-induced Femoral Head Necrosis（SIFHN）. Methods：The Japanese rabbits of 12 -18 weeks old and 2.5±0.6 kg, were randomly divided into 3 groups： The control guoup （Group A：n=6） were fed with standard forage and fodder while the experimental group（Group B：n=14） were injected by 2.5 mg/kg ·d^-1 with DEX intramuscularly. The intervention group （Group C： n=14） were also injected by 2.5 mg/kg· d^-1 DEX intramuscularly and given Pravastatin 2.5 mg/kg · d^-1. Simultaneously, penicillin-natrium 800 000 U and streptomycin 1.0g were injected to every rabit twice a week to avoid infection. At the beginning of experiments all the rabbits and every following 6^th, 8^th, 10^th and 12^th weeks 3 rabbits of each group, before they were executed, they were examined for their levels of serum cholesterol and triglyceride, Prothrombin Time（PT） and tissue plasminogen（t-PA）. The specimens of double femoral heads were taken to be studied under light microscope and the osteocytes apoptosis was measured by means of TUNEL. Result：The levels of serum cholesterol and triglyceride of the Group C was much lower than that of Group B, PT is lower and t-PA is higher than that of Group B since 6 weeks （ P〈0.05）. The analysis of apoptosis show that the AI （Apoptosis Index） was lower than Group B （ P 〈0.01）. Conclusion： The Dexamethasone resulted in building up the model of rabbits＇ SIFHN as in Group B. and the Pravastatin can intervene the apoptosis of osteocytes in the course of SIFHN effectively. The mechanism of which might be related to anti-liemicing, anti-coagulation and the expression of the apoptosis regulators.