阿法骨化醇对SD大鼠骨合成的影响

The preventive effect of alfacalcidol on cancellous and cortical bone in intact female SD rats

目的观察不同剂量的阿法骨化醇对8月龄未交配♀SD大鼠骨组织形态计量学的影响,并探讨阿法骨化醇对大鼠皮质骨和松质骨影响的差异性。方法阿法骨化醇分别按0.005、0.025、0.05、0.1μg·kg-1·d-14种不同剂量,连续给大鼠灌胃120d,同时设棉籽油空白对照组和基础组。120d后处死大鼠,取右侧胫骨上端和中段不脱钙骨组织包埋、磨片、染色,进行骨组织形态计量学测量和计量。结果阿法骨化醇0.1μg·kg-1·d-1治疗组与棉籽油空白对照组比较,胫骨上段骺端松质骨骨小梁面积百分数(%B.Ar)增加,骨小梁的宽度(Tb.Wi)升高,骨小梁的分离度(Tb.Sp)下降;增加骨芽的形成;松质骨量呈剂量依赖性增加;皮质骨骨外膜面荧光周长百分数(%Ps-L.Pm)明显增加,骨表面骨形成率(Ps-BFR/BS)上升;骨内膜面荧光周长百分数(%En-L.Pm)明显下降和骨内膜面吸收周长(%En-Er.Pm)下降,但皮质骨骨量的增加不明显。结论对正常8月龄未交配♀SD大鼠给予0.1μg·kg-1·d-1阿法骨化醇灌胃120d,具有促骨合成作用,表现在刺激皮质骨骨外膜的骨形成和促进松质骨骨芽形成,大鼠松质骨骨量增加。而抗骨吸收作用表现在抑制骨小梁骨表面和皮质骨骨内膜面的骨吸收,且抑制骨吸收作用大于骨形成,产生正性的内膜骨平衡状态。阿法骨化醇对松质骨的效应明显强于皮质骨。

Aim To investigate Alfacalcidol[1α（OH） D 3 ]on cancellous and cortical bone histomorphometric changes of both the longitudinal sections of proximal tibial metaphyses and cross-sections of tibial shaft in intact female rats.Methods Seventy-four,8.5-month-old intact female rats were orally treated with 0.005,0.025,0.05 and 0.1μg·kg-1 of alfacalcidol for 120 days.After 120 days,rats were autopsied for the tibial bone;histomorphometric analyses of the PTM,tibial shaft（TX） ex vivo were performed.Results Histomorphometric analysis showed that 0.1μg ·kg -1 alfacalcidol treatment increased trabecular bone mass（%Tb.Ar） and trabecular width（Tb.Wi） ,decreased trabecular separation（Tb.Sp） ;dynamic data showed 0.1μg·kg -1 alfacalcidol treatment decreased bone turnover（BFR/BV） ,suppressed trabecular and endocortical bone resorption（%Er.Pm） ,suppressed bone resorption more than bone formation（BFR/BS） on endosteal surface,stimulated trabecular＂bone bouton＂and periosteal bone formation.Conclusions With 0.1μg·kg -1 Alfacalcidol treatment for 3 months,cancellous bone volume increased significantly,with increased trabecular thickness and connectivity,decreased trabecular separation,and elevated bone strength;The bone gain was partly due to stimulating ＂bone buds＂formation and periosteal bone formation. Alfacalcidol had anabolic effect resulting from minimodeling and mixed remodeling/minimodeling-induced bone gain;Alfacalcidol treatment increased cancellous bone mass more than cortical bone mass and had sitespecific effect.