目的 评价淫羊藿醇提物对去除卵巢致骨质疏松大鼠的治疗作用,初步探讨其作用机制。方法 SD大鼠切除双侧卵巢,造成骨质疏松大鼠模型。手术4周后,以阳性药依普黄酮片(200 mg/kg)和不同剂量的淫羊藿醇提物(170、85 mg/kg)连续ig给药8周,然后取血清测定其碱性磷酸酶(ALP)和抗酒石酸酸性磷酸酶(StrACP)活性;采用免疫组化法测定股骨中骨保护素(OPG)、破骨细胞分化因子(RANKL)蛋白表达;采用三点弯曲法测定其胫骨的生物力学性质;最后运用micro-CT对股骨远端的骨小梁参数进行分析,并对其进行三维重建,得到骨小梁的3D图形来直观地说明淫羊藿醇提物对骨质疏松大鼠的作用。结果 淫羊藿醇提物高剂量组不仅能够显著降低血清ALP和StrACP活性,还能显著增加OPG蛋白表达,降低RANKL蛋白表达,且能有效地改善胫骨生物力学性质和股骨骨小梁参数。结论 淫羊藿醇提物高剂量(170 mg/kg)对骨质疏松大鼠具有明显的治疗作用,其可能是通过促进成骨细胞活性、抑制破骨细胞活性来实现的。

Objective To study the therapeutic effect and mechanism of alcohol extract from Epimedii Herba (AEEH) on ovariectomy-induced osteoporosis in rats. Methods Ipriflavone Tablets (200 mg/kg) and different doses of AEEH (170 and 85 mg/kg) were given for 8 weeks by ig administration, from 4 weeks after ovariectomization. Then, the protein expression of serum ALP, StrACP, femoral osteoprotegerin (OPG), and osteoclast differentiation factor (RANKL) was evaluated by biochemical assay kits and immunohistochemical evaluation; The mechanical properties of the tibia were determined by three point bending test method. Finally, the distal femoral trabecular bone parameters and the 3D reconstruction, trabecular bone of the 3D graphics were intuitively illustrated, and the effect of AEEH on rats suffered from osteoporosis role was observed by micro-CT. Results Treatment with AEEH (170 mg/kg) significantly inhibited serum ALP and StrACP levels. Furthermore, AEEH also could significantly increase OPG protein expression while reduce RANKL protein expression compared with OVX rats. In addition, it could effectively improve the biomechanical properties of the tibia and the parameters of the trabecular bone of the femur, respectively. Conclusion AEEH is effective in treating ovariectomy-induced osteoporosis in rats and the mechanism is mainly achieved by promoting the activity of osteoblast and inhibiting the activity of osteoclast.

国家自然科学基金资助项目(81303275,81503265);2013苏州市医疗器械与新医药专项(ZXY2013022)