丹参骨髓腔内注射预防激素性股骨头坏死的可能性

Preventive effects of intramedullary injection with salvia miltiorrhiza on steroid-induced necrosis of the femoral head

背景:由于股骨头缺血性坏死的确切发病机制尚不清楚,其治疗方法尚不理想。目的:观察丹参注射液骨髓腔内注射预防激素性股骨头缺血性坏死的可行性和机制。设计、时间及地点:随机对照动物实验,细胞病理学观察,于2005-04/2007-05在遵义医学院完成。材料:健康家兔30只,雌雄各半,6月龄,体质量(2.5±0.25)kg,随机分为对照组、模型组、预防组,每组10只。丹参注射液。方法:对照组臀肌注射生理盐水。模型组臀肌注射醋酸泼尼松龙,每次7.5mg/kg,每周2次,共8周。预防组臀肌注射醋酸泼尼松龙制作糖皮质激素诱导激素性股骨头坏死动物模型,同时采用髂骨穿刺针在股骨第三转子尖下方0.3～0.5cm处由外向内上方穿入后注入丹参注射液,每侧0.4mL/kg,每周2次,共8周。主要观察指标:观察3组家兔血脂、血钙磷、X射线、发射型计算机断层扫描及组织病理学指标的变化。结果:模型组血清钙和钙磷乘积明显降低,X射线示股骨头密度不均,可见大小不一的囊状透亮区,部分骨小梁模糊不清,但股骨头保持完整,关节间隙正常;发射型计算机断层扫描显示股骨头在血流、血池相放射性分布稀疏,延迟相放射性异常浓聚;组织病理学观察显示,股骨头骨皮质变薄,骨小梁变细,结构紊乱,骨髓明显坏死和脂肪化,空骨陷窝率明显增多。预防组血清钙、血清钙磷乘积升高;X射线示除骨小梁略微不清外,股骨头形态和骨密度均接近正常;发射型计算机断层扫描显示动态与静态图像已接近正常兔核素放射性骨显像结果;组织病理学观察显示,骨小梁变细不明显,排列较规则,陷窝内骨细胞数量稍有减少,细胞核固缩边聚现象不严重,空骨陷窝数量较模型组明显减少。结论:复方丹参注射液可通过改善血液流变学、降低空骨陷窝率而产生对股骨头缺血性坏死的预防作用。

BACKGROUND： The pathogenesis of avascular necrosis of the femoral head is still uncertain, so the treatment is not favorable. OBJECTIVE： To study the feasibility and mechanism of intramedullary injection with salvia miltiorrhiza for preventing of steroid-induced necrosis of the femoral head. DESIGN, TIME AND SETTING： Randomized controlled animal trial was performed at Zunyi Medical College between April 2005 and May 2007. MATERIALS： Thirty 6-month-old healthy rabbits, half amount of male and female, weighing （2.5±0.25） g, were randomly divided into three groups （n=10）： control, model, and prevention groups. METHODS： Normal saline was injected into the control group. Prednisolone was injected into model group, 7.5 mg/kg, two times per week for 8 weeks. Glucocorticoid-induced animal model in the prevention group was intramedullary injected with salvia miltiorrhiza, 0.3-0.5 cm below the third trochanter of the femur, 0.4 mL/kg, twice a week for 8 weeks. MAIN OUTCOME MEASURES： Blood lipids level, serum calcium and phosphorus were measured; X-ray, emission computerized tomographic （ECT） and histopathology were performed. RESULTS： The serum calcium and phosphorus in model group were remarkably reduced. X-ray showed inhomogeneous density of the femoral head, with irregular radiolucent area, obscure structures of bone-trabecula, but intact femoral head and normal joint space. The blood flow and blood pool showed decreasing radioactive distribution of the femoral head, and local concentration of nuclide in the delayed phase in the model group. Histopatholgical observation suggested that the cortical bone was thinned, with thin bone-trabecula and irregular arrangement, necrosed bone marrow and pimelosis and increased bone lacuna. The calcium-phosphorus product of prevent group was increased; X-ray showed normal femoral head appearance and normal bone density except unclear bone-trabecula. ECT showed the dynamic and static images of the prevention group were similar as normal imaging of rabbits. In addition, histopatholgical observation suggested the rate of empty lacuna was decreased, and bone trabecula minimally thinned with ordered arrangement. CONCLUSION： Salvia miltiorrhiza injection plays a good effective role in the prevention of steroid-induced avascular necrosis of femoral head through improving hemorheology and reducing rate of empty lacuna.