目的 探讨巴戟天寡糖对环磷酰胺（cyclophosphamide，CTX）诱导骨质疏松雄性小鼠氧化应激指标和股骨组织形态的影响，并探析炮制工艺对巴戟天寡糖成分及效用的影响。方法 对巴戟天寡糖及酒巴戟天寡糖中成分进行提取分离并验证。将雄性昆明小鼠随机分为对照组、模型组、维生素D₃（5 μg/kg）组及巴戟天寡糖低、高剂量（50、200 mg/kg）组和酒巴戟天寡糖低、高剂量（50、200 mg/kg）组。除对照组外，其余小鼠连续15 d ig CTX（4.5 mg/kg）制备骨质疏松模型，造模结束后，给予相应药物干预4周，测定各组小鼠血清中谷胱甘肽过氧化物酶（glutathione peroxidase，GSH-Px）、过氧化氢酶（catalase，CAT）活性和丙二醛（malondialdehyde，MDA）水平；采用Micro-CT对股骨远端骨微结构进行分析；采用三点弯曲法测定骨生物力学参数；制片测量骨组织形态计量学参数。结果 巴戟天寡糖及酒巴戟天寡糖的6种寡糖成分的含量不同，巴戟天寡糖中D-果糖、蔗糖、1-蔗果三糖、耐斯糖、1F-果呋喃糖基耐斯糖的含量较酒巴戟天寡糖更多，而酒巴戟天寡糖中D(+)-无水葡萄糖的含量更多。与模型组相比，巴戟天寡糖低剂量组小鼠股骨的骨密度显著增加（P＜0.01）；骨生物力学参数改善（P＜0.05、0.01）；血清MDA水平降低（P＜0.05）；松质骨的骨小梁面积比（percentage of trabecular bone area，Tb.Ar）、荧光标记周长比（percentage of fluorescent label perimeter，L.Pm）、骨矿化沉积率（mineral apposition rate，MAR）及骨形成率（bone formation rate to bone volume，BFR/BV）显著升高（P＜0.05、0.01），骨小梁分离度（trabecular separation，Tb.Sp）和破骨细胞数目（number of osteoclast，OC.N）显著降低（P＜0.01）；皮质骨的MAR显著降低（P＜0.05），BFR/BV显著升高（P＜0.01）。巴戟天寡糖高剂量组小鼠骨密度显著增加（P＜0.01）；血清中CAT活性显著升高（P＜0.01）；松质骨组织中Tb.Ar显著升高（P＜0.05），Tb.Sp显著降低（P＜0.05）。酒巴戟天寡糖低剂量组小鼠骨密度显著增加（P＜0.01）；骨生物力学参数改善（P＜0.05）；血清GSH-Px活性升高（P＜0.01）；松质骨的Tb.Ar、L.Pm、MAR及BFR/BV显著升高（P＜0.05、0.01），Tb.Sp和OC.N显著降低（P＜0.05、0.01）；皮质骨的MAR显著降低（P＜0.05），BFR/BV显著升高（P＜0.05）。酒巴戟天寡糖高剂量组小鼠血清中CAT活性显著升高（P＜0.01），对于骨结构改变则无明显影响作用。结论 不同炮制工艺会影响巴戟天寡糖的成分含量。巴戟天寡糖及酒巴戟天寡糖均能不同程度地改善氧化应激指标，但低剂量的巴戟天寡糖及酒巴戟天寡糖对于改善CTX引起的骨质疏松的作用更为显著。

Objective To investigate the effects of Morinda officinalis oligosaccharides (MO) on oxidative stress indexes and femoral tissue morphology in male mice with cyclophosphamide (CTX)-induced osteoporosis, and explore the effects of processing technology on the composition and efficacy of MO. Methods The components in MO and wine M. officinalis oligosaccharides (WMO) were extracted, separated and verified. Male Kunming mice were randomly divided into control group, model group, vitamin D₃ (5 μg/kg) group, MO low-and high-dose (50, 200 mg/kg) groups, WMO low-and high-dose (50, 200 mg/kg) groups. Except for control group, the other mice were continuously ig CTX (4.5 mg/kg) for 15 d to establish osteoporosis models. After the modeling, mice were given corresponding drug for 4-week intervention, glutathione peroxidase (GSH-Px), catalase (CAT) activities and malondialdehyde (MDA) level in serum of mice in each group was measured; Micro-CT was used to analyze distal femur bone microstructure; Three-point bending method was used to determine bone biomechanical parameters; Slices were used to measure bone histomorphometric parameters. Results MO and WMO had different contents of six kinds of oligosaccharides. Contents of D-fructose, sucrose, 1-fructose, nystose and 1F-fructofuranosylnystose in MO was higher than that of WMO, while content of D(+)-anhydroglucose was higher in WMO. Compared with model group, bone mineral density of femur of mice in WO low-dose group was significantly increased (P < 0.01), bone biomechanical parameters were improved (P < 0.05, 0.01), MDA level in serum was decreased (P < 0.05); Percentage of trabecular bone area (Tb.Ar), percentage of fluorescent label perimeter (L.Pm), mineral apposition rate (MAR) and bone formation rate to bone volume (BFR/BV) in cancellous bone were significantly increased (P < 0.05, 0.01), trabecular separation (Tb.Sp) and number of osteoclasts (OC.N) were significantly decreased (P < 0.01); MAR in cortical bone was significantly decreased (P < 0.05), and BFR/BV was significantly increased (P < 0.01). Bone mineral density of mice in MO high-dose group was significantly increased (P < 0.01), CAT activity in serum was significantly increased (P < 0.01), Tb.Ar in cancellous bone tissue was significantly increased (P < 0.05), Tb.Sp was decreased (P < 0.05). Bone mineral density in WMO low-dose group was significantly increased (P < 0.01), bone biomechanical parameters were improved (P < 0.05), GSH-Px activity in serum was increased (P < 0.01); Tb.Ar, L.Pm, MAR and BFR/BV in cancellous bone were significantly increased (P < 0.05, 0.01), Tb.Sp and OC.N were significantly decreased (P < 0.05, 0.01); MAR in cortical bone was significantly decreased (P < 0.05), BFR/BV was significantly increased (P < 0.05). CAT activity in serum of mice in WMO high-dose group was significantly increased (P < 0.01), but had no significant effect on the changes of bone structure. Conclusion Different processing techniques can affect the content of MO. MO and WMO can improve oxidative stress indicators to varying degrees, but effect of low dose MO and WMO on improving CTX-induced osteoporosis are more significant.

R285.5

国家自然科学基金资助项目（82074007）