柚皮苷促进成骨细胞分化并有效改善卵巢切除所致的骨质疏松

Naringin promotes osteoblast differentiation and effectively reverses ovariectomy-induced osteoporosis

目的评价柚皮苷对成骨细胞增殖与分化的作用,并采用大鼠骨质疏松模型评价柚皮苷的治疗效果。方法采用不同浓度的柚皮苷处理大鼠骨髓基质细胞,观察其增殖、分化与功能的改变。采用低、中、高三种不同剂量的柚皮苷作为治疗组,磷酸缓冲液(PBS)作为对照组,对卵巢摘除诱发骨质疏松的大鼠灌胃2个月。应用骨质疏松大鼠右侧股骨的X线照片和显微CT扫描测量骨矿密度以及骨体积分数,使用骨质疏松大鼠左侧胫骨的病理切片检测组间骨小梁厚度和骨小梁间隙的变化。结果体外研究表明柚皮苷可有效增加骨髓基质细胞的增殖和成骨分化,浓度为10μg/ml时对骨钙素的表达具有最显著的作用。骨髓基质细胞对柚皮苷的治疗呈现一种延迟反应模式。柚皮苷并有效逆转了卵巢切除导致的骨质疏松,增加了骨密度、骨容量和骨小梁厚度。300 mg/kg(中剂量)是具有满意治疗效果的最优剂量。结论柚皮苷促进骨髓基质细胞的分化与增殖,增加骨钙素的表达,它能有效逆转卵巢切除大鼠的骨质疏松过程。本研究表明柚皮苷是治疗骨质疏松的潜在有效药物。

Objective To eva]uate the effect Of naringin on osteoblast differentiation and proliferation; and to assess its therapeutic efficacy on rat osteoporosis model. Methods Rat bone marrow stromal cells （BMSCs） were firstly treated with different concentrations of naringin. Then the changes of proliferation, differentiation, and functions of were observed. Ovariectomy （OVX） -induced osteoporotie rats in treatment groups were given a gavage of low, medium, or high dosage of naringin daily for 2 months, while rats in control group received a gavage of PBS for 2 months. Bone mineral density （BMD） and BV/TV （bone volume/total volume） of the right femurs was detected using X-ray imaging and micro-CT scanning. The changes of trabecular thickness （Tb. Th） and trabecular space （Tb. Sp） among groups were observed using pathological sections of the left tibias. Results Naringin was effective on enhancing the proliferation and osteogenic differentiation of the BMSCs, and 10 p.g/ml naringin had the most significant effect on osteocalcin expression in vitro. A delayed response pattern of BMSCs to the naringin treatment was observed. Naringin effectively reversed OVX-indueed osteoporosis, and naringin increased BMD, bone volume, and trabecular thickness. The medium dosage （300 mg/kg） appeared to be the optimal dosage with satisfying therapeutic effects. Conclusion Naringin promotes the proliferation and differentiation of the BMSCs, and increases osteocalcin expression. It can effectively reverse the ovariectomy-indueed osteoporosis in rats. This study suggests that naringin is a potent therapeutic drug for the treatment of osteoporosis.