不同双磷酸盐药物在联合“骨康灵”治疗中对股骨头坏死的疗效研究

Experimental study on the therapeutic effect of Gukangling combined with different bisphosphonates on aseptic necrosis of the femoral head

目的探讨不同双磷酸盐药物联合"骨康灵"治疗兔股骨头无菌性坏死(ANFH)模型的疗效分析。方法采用肌肉注射地塞米松磷酸钠方法制作ANFH动物模型;制作动物模型成功后,将实验兔设为A组(正常对照组)、B组(ANFH对照组)、C组("99Tc-MDP"治疗组)、D组("阿仑膦酸钠"治疗组)、E组("骨康灵"治疗组)、F组("99Tc-MDP"联合"骨康灵"治疗组)和G组("阿仑膦酸钠"联合"骨康灵"治疗组),疗程为16周,后比较各组之间骨密度、影像学及生化指标变化并评价疗效。采用SPSS17.0软件进行统计学处理。结果 ANFH模型组与正常组比较显示:骨组织病理学、99mTc-MDP骨显像,骨密度、骨生物力学、骨形态计量、ALP、BGP均有明显差异(P<0.01)。经过不同药物联合治疗后,C、D、E、F、G组经治疗后与B组相比,骨组织病理学、99mTc-MDP骨显像,骨密度、骨生物力学、骨形态计量、ALP、BGP均比B组有有明显统计学意义;疗效评判结果显示:F组为显效基本接近A组,C组、G组和D组均为有效,但E组疗效相对不明显。结论药物"99Tc-MDP"联合联合"骨康灵"治疗骨质疏松效果优于其他药物治疗;因此,中草药联合"99Tc-MDP"可能成为治疗骨质疏松的有效治疗方法。

Objective To investigate the effect of 2 types of bisphosphonates combined with Gukangling decoction on the treatment of aseptic necrosis of the femoral head （ANFH） in a rabbit model. Methods Animal experiment included 2 stages, model establishment and grouping therapy. In the first stage, rabbit ANFH model was established by intramuscular injection of dexamethasone （DX） for 8 weeks. After 8 weeks, bone histopathology, bone mineral density （BMD）, bone biomechanics, X- ray, CT, region of interest ratio （ROI ratio） on 99mTc-MDP bone scans, and serum bone alkaline phosphatase （BALP） and osteocalcin （BGP） were detected and analyzed to evaluate the successful establishment of the rabbit ANFH model. In the second stage, rats were divided into group A （normal control） , group B （ANFH control） , group C （ANFH treated with99 Tc-MDP）, group D （ANFH treated with alendronate sodium）, group E （ANFH treated with Gukangling decoction） , group F （ANFH treated with99 Tc-MDP and Gukangling decoction） , group G （ANFH treated with alendronate sodium and Gukangling decoction）. After 16- week treatment, the above indexes were detected and analyzed to evaluate the therapeutic effect. Statistic analysis was performed using SPSS 17.0. Results Histopathology results in the first stage demonstrated that the trabeculae displayed regularly without bone destruction in rats of group A. However, in group B the bone trabeculae were sparse and ruptured. BMD and biomechanical parameters were declined. 99mTc-MDP was significant uptaken at the femoral head in and BALP and BGP increased, indicating the rabbit model of ANFH was established successfully. In the second stage, histopathology results were similar to the first stage in group A and B. Bone trabeculae were significantly restored in group F, almost similar to group A. Bone trabeculae were also restored in group C, D, and G comparing to those in group B. In group E, density of bone trabeculae slightly increased, while the trabecular bone repair was not obvious. Results of BMD, bone morphology, bone biomechanics, biomechanical parameters, femoral head ROI ratio on 99mTc-MDP bone scan, BALP, BGP, and bone mineral deposition in different groups changed in various degrees. Relative efficacy evaluation results showed that group F was markedly effective, group C, D, and G were effective, but group E was not obviously effective. Conclusion 99 Tc-MDP combined with Gukangling decoction shows markedly therapeutic effect, and the maximal effect is achieved in group F, indicating that 99Tc-MDP combined with right recipe of Chinese herbal medicine may have great value in the treatment of ANFH.