联合应用阿托伐他汀和氯吡格雷对激素性股骨头缺血性坏死的早期干预作用

Early intervention for steroid-induced avascular necrosis of femoral head with combined use of atorvastatin and clopidogrel in rabbits

背景:目前激素性股骨头缺血性坏死(SANFH)病例较多,手术干预方法多样,保守治疗方法较少。目的:研究联合应用阿托伐他汀和氯吡格雷对SANFH兔动物模型的血脂及血浆黏度的影响,探讨联合用药对预防及治疗SANFH的可行性和机制。方法:将24只健康成年新西兰大白兔随机分为3组各8只:A组为模型组,采用Kabata造模法(第1周经耳缘静脉注射马血清10 ml/kg,间隔3周后注射第2次马血清,第5周时连续3 d腹腔内注射地塞米松磷酸钠10 mg/kg·d)制作SANFH模型;B组为治疗组,造模法同模型组,腹腔注射激素后每日给予抗凝药物氯吡格雷4 mg/kg和降脂药阿托伐他汀3 mg/kg灌胃;C组为对照组,马血清注射方法同模型组,而第5周时改为连续3 d腹腔内注射生理盐水4 ml/kg·d。各组分别于实验前、第5周注射激素或生理盐水后、第6周、第8周及第10周检测血清胆固醇、甘油三酯及血浆黏度,并行X线片检查及股骨头与肝脏病理切片观察病变情况。结果:模型组和治疗组的血清胆固醇、甘油三酯含量及血浆黏度均显著高于对照组,模型组的血清胆固醇、甘油三酯含量及血浆黏度显著高于治疗组,两两比较均有统计学差异(P<0.05),提示药物早期干预有效。通过X线片检查及病理切片可见治疗组股骨头坏死发生率明显低于模型组,而对照组未出现股骨头坏死。结论:联合应用阿托伐他汀和氯吡格雷可以明显抵消激素对血脂和血浆黏度的影响,可能对预防SANFH具有一定作用。

Background： Steroid-induced avascular necrosis of the femoral head （SANFH） is usually treated by surgical methods. How- ever, there are few reports on expectant treatment for the disease. Objective： To study the effects of combined application of atorvastatin and clopidogrel on blood fat and viscosity of SANFH rabbits, and to investigate the feasibility and mechanism of medicine intervention for precaution and treatment of SANFH. Methods： Twenty-four healthy adult New Zealand white rabbits were randomly divided into three groups （n=8）： model group, treatment group, and control group. SANFH rabbit models were established by the Kabata method in model group and treatment group （10 ml/kg equine serum was injected into ear-vein on week 1 and 4 of the study, then 10 mg/kg, d dexa- methasone sodium phosphate was injected intraperitoneally for 3 days on week 5）. After that, in the treatment group, rabbits was intragastrically administrated with 4mg/kg of clopidogrel and 4mg/kg. d atorvastatin daily. In the control group, 10 ml/kg equine serum was injected into ear-vein on week 1 and 4 of the study, and 4 mg/kg- d normal saline was injected intraperitone- ally for 3 days on week 5. Serum cholesterol, triglyeride and plasma viscosity were tested before experiment and ond week 5, 6, 8, and 10 of the experiment. The changes of femoral head and liver were observed through X-ray and pathological section. Results： Compared with those in the control group, serum cholesterol, triglyeride and plasma viscosity of model group and treatment group were significantly increased （P〈0.05）. The above-mentioned parameters in the model group were significant- ly higher than those in the treatment group （P〈0.05）. The results of X-ray and pathological section showed that the incidence of SANFH of treatment group was obviously lower than that of model group, and no ONFH was found in the control group. Conclusions： Atorvastatin and clopidogrel application can obviously decrease blood viscosity and fat metabolic disorder in SANFH rabbits, which maybe contribute to prevent SANFH.