动态观察去卵巢骨质疏松大鼠股骨骨微结构的变化

Dynamic Change of Trabecular Bone Microarchitecture in the Ovariectomized Osteoporosis Rats

目的:绝经后骨质疏松是好发于中老年女性人群中的骨代谢疾病,去卵巢骨质疏松大鼠模型是国内外通用的模拟绝经后骨质疏松发生的经典动物模型,本研究通过观察去卵巢骨质疏松大鼠股骨骨微结构的动态变化,为骨质疏松大鼠模型的临床应用提供理论参考依据。方法:将90只3月龄雌性SD大鼠按体重分层后随机分为基础组(10只)、假手术组(40只)和去卵巢组(40只)。分别在手术前(基础组)和后的3、6、12、24周,腹主动脉取血处死基础组以及假手术组和去卵巢组大鼠,每组各8-10只。每组中随机取6只大鼠,对其左股骨行micro-CT扫描及三维结构重建。选择股骨远端距生长板远端1 mm处,2.0 mm×3.5 mm,厚0.9 mm的骨组织为感兴趣区域,对感兴趣区域进行骨形态计量学分析。结果:与0周组比较,从去卵巢3周开始一直持续到24周,去卵巢组大鼠股骨vBMD、BV/TV和Tb.N显著降低,Tb.Sp和SMI显著升高,而Tb.Th无显著变化;与0周组比较,从假手术后3周开始一直到24周,假手术组所有检测指标均无显著变化。与同周龄假手术组比较,从去卵巢3周开始一直持续到24周,去卵巢组大鼠股骨Tb.N、BV/TV和vBMD显著降低,Tb.Sp显著升高,而Tb.Th没有显著变化。从去卵巢6周开始一直到24周,去卵巢组大鼠SMI显著增加。结论:3月龄大鼠股骨远端的骨微结构在去卵巢3周时就出现显著变化。提示,采用3月龄大鼠进行抗骨质疏松药物筛选时,去卵巢3周后就可以进行药物处理。

Objective： Postmenopausal osteoporosis is a kind of metabolic bone disease occurred in middle-aged women. Ovariec- tomized rat model is a classic animal model to simulate postmenopansal osteoporosis. The dynamic change of trabecular bone microar- chitecture in the ovariectomized （OVX） osteoporosis rats is investigated in this paper. This provides a theoretical basis for the clinical ap- plication of ovariectomized rat model. Methods： Ninety 3-month-old Spraque-Dawley female rats were used. Forty rats underwent ova- riectomy, and forty received sham surgery. Ten animals without any surgery were sacrificed at week 0 to serve as the baseline group. Eight to ten animals in both OVX and sham group, respectively, were euthanized at week 3, 6, 12 and 24 post-surgery. The femur mi- croarchitecture was detected by micro-CT in vitro and a three- dimensional model was rebuilt. The osseous tissue, which was around 1 mm from the distal femur, was selected as the region of interest with 2.0 mm in length, 3.5 mm in width and 0.9 mm in thickness and this region was analyzed with bone morphometry. Results： From third week post surgery until twenty-forth week post surgery, Miero-CT re- vealed the number of trabecular bone （Tb.N）, the fraction of bone tissues （BV/TV）, as well as the volume bone mineral density （vBMD） in distal femur of OVX group were significantly lower than that in the baseline group. Whereas the separation of trabecular bone （Tb.Sp） and the bone structure index （SMI） were significantly higher than that in the baseline group. There were no significant changes in all mi- crostructure parameters of the sham group. The vBMD, BV/TV and Tb.N in distal femur of OVX group were significantly lower than that in the sham group with the same age, while the Tb.Sp was significantly higher than that in the sham group. From the sixth weeks until 24 weeks, the SMI of OVX group increased significantly. There was no difference in the thickness of trabecular bone （Tb.Th） during four chosen periods. Conclusion： The femur trabecular bone microarchitecture changed significantly from 3 weeks after OVX in 3-month fe- male rats. The 3-month-old rats ovariectomized after 3 weeks could receive the drug intervention to screening anti-osteoporosis drugs.