维甲酸致小鼠骨质疏松模型的量效关系及骨药理作用探讨

Bone loss (osteoporosis)induced by retinoic acid in mice and its dose-dependent effects

目的 观察不同剂量维甲酸致小鼠骨质疏松的量效关系 ,探讨维甲酸性骨质疏松的的骨代谢作用特点及骨药理学作用机制。方法 用 3种剂量维甲酸造成小鼠骨丢失为主的骨质疏松模型 ,监测体重 ,2wk后处死小鼠 ,取肝、脾、胸腺称重 ,并取股骨进行骨干重、骨钙、磷、镁、锌、锰、硫及骨羟脯氨酸 (B HOP)的测定和比较。结果 不同剂量维甲酸均分别致小鼠骨干重减少 ,骨横短径减少 ,骨基质的主要成分骨羟脯氨酸 (HOP)减少 ,骨矿物质也有不同程度的减少 ;骨HOP及骨钙的减少与骨干重的比值密切相关 ,但骨磷、镁、锌的减少呈非等比例性减少 ,尤以骨锌明显。结论 维甲酸 3种剂量均可引起小鼠以骨量丢失为主的骨质疏松 ,并呈量效关系 ,其特征是骨钙及骨羟脯氨酸等比例性丢失 ,早期以骨磷、镁、锌的明显丢失为主 。

AIM To study the dose dependent effects on osteoporosis induced by retinoic acid(RA) and to analysis the metabolic characteristics of bone. METHODS Three dosages of retinoic acid were given to the mice for 2 weeks while the body weight(BW) were measured once a week. At the end, femoral dry weight, Bone hydroxyproline, calcium content, Phosphor, Magnesium, Zinc, Manganese and Sulphonium of femora were measured. RESULTS Compared with normal control mice, three dosages of retinoic acid can induce the decrease of femoral dry weight and the short transverse diameter of femoral, Bone hydroxyproline content decreased remarkably, and so did the bone mineral. The Bone HOP and Bone Ca content was coincident with the femoral dry weight, but the lessening of Bone P, Bone Mg, Bone Zn and Bone Mn became inverse ratio with the femoral dry weight, particularly that of the Bone Zn. CONCLUSION Three dosages of retinoic acid in mice can induce osteoporosis with the lessening of bone mass, which characteristics were the losing of Bone HOP and the Bone Ca content in geometric proportion. The levels of Bone P, Bone Mg, and Bone Zn had lost remarkably in the early time, the Bone Zn may play importance function in osteoporosis model induced by retinoic acid.