泼尼松致大鼠骨质疏松症的作用机制研究

目的观察长期超生理剂量应用泼尼松对大鼠主要负重骨的影响以及所造成的骨质疏松症的特点,并探讨其作用机制。方法SD大鼠予泼尼松按1、3、9mg·kg-1灌胃,每日1次,连续12wk。实验结束后取尺骨测定骨中羟脯胺酸(Hyp)、钙(Ca2+)、磷(P3+)含量;取胫骨做不脱钙骨切片进行骨形态计量学检查,取股骨测定骨的物理生长指标以及生物力学指标来观察糖皮质激素长期超生理剂量应用对大鼠骨质的影响。结果与Cot组比,PrH组、PrM和PrL组反应骨量的指标的%Tb.Ar分别下降46.38%,41.40%和9.75%;Tb.N下降64.04%,52.74%和2.74%;Tb.Th下降29.81%,21.96%和6.05%,反映骨吸收的指标Oc.N/BV分别上升了274.0%,236.08%和77.85%;%Oc.pm上升了161.17%,190.95%和68.38%。反映单位骨组织形成率BFR/TV明显下降45.84%,39.96%和6.08%。PrH组和PrM组大鼠骨重,Hyp含量和Ca2+/P3+比值明显降低(P<0.05),骨髓腔中出现了明显的脂肪化。结论予大鼠按3或9mg·kg-1长期灌喂泼尼松可造成明显的骨质丢失,其机制可能与泼尼松促进骨吸收抑制骨形成以及与其促进骨髓脂肪化,增加骨内压有关。

The mechanism of osteoporosis induced by prednisone

Aim To investigate the mechanism of osteoporosis induced by long-term administration of prednisone.Methods Forty SD rats were randomly divided into 4 groups with 10 rats per group.Group 1 was treated orally with vehicle as control, other groups were oral gavages prednisone (1,3 mg·kg-1or 9 mg·kg-1), once a day for 12 weeks.At the experimental endpoint, the undecalcified longitudinal proximal tibia was cut for osteoclasts analysis and for the cancellous bone histomorphometric and fluorochrome labeling analysis,the desiccant left ulnar was used for testing the content of Ca2+ and hydroxyproline.Length and width of the thighbone were tested to observe the instance of bone growth.Results Compared with control group, the %Tb.Ar reduced by 46.38%,41.40% and 9.75% respectively in group PrH、PrM and PrL.Tb.N reduced by 64.04%,52.74% and 2.74%;Tb. Th reduced by 29.81%,21.96% and 6.05% respectively.But Oc.N/BV increased by 274.0%,236.08% and 77.85%;%Oc.pm increased by 161.17%,190.95% and 68.38%. Contents of bone hydroxyproline and Ca2+/P3+ decreased remarkably in group PrH and PrM,and the fat was showed markedly in the marrow of the prednisone group.Conclusions Bone loss occured in four-month-old male Sprague-Dawley rats after prednisone-treated for 12 weeks in the dose of 3 mg·kg-1 or 9 mg·kg-1. The mechanism may be related to the fact that prednisone can stimulate osteoclast,inhibite osteoblast, and increase the fat cell in bone marrow.