双侧卵巢切除大鼠不同时间段骨形态计量学参数的观察

Study of bone histomorphometric changes at regular intervals in OVX rats

目的观察去卵巢大鼠骨质疏松模型复制情况并动态观察去卵巢后不同时间段骨丢失情况,为抗骨质疏松药物研究提供对照依据。方法4.5月龄SD雌性大鼠,按体重随机分组,大鼠摘除双侧卵巢;在实验的第0d(4.5月龄)、4w(5.5月龄)、12w(7、5月龄)、18w(9.5月龄)杀死大鼠取材;采用体内双荧光标记法,胫骨上段硬组织包埋切片及松质骨形态计量学分析处理,观察去卵巢后不同时间段骨丢失情况。结果大鼠去卵巢4w后骨量显著降低,骨结构变差,骨形成有增加,骨吸收增加,骨吸收大于骨形成,骨转换增加。去卵巢12w后,大鼠骨量进一步降低,骨小梁宽度先变窄(4w)后变宽(8、12、18w),骨形成和骨吸收均增加,去卵巢后大鼠在前一个月内(4w)骨量(Tb.Ar%)降低64.18%,差异有显著性(P<0.05)。结论大鼠去卵巢4w后骨量降低,骨结构变差,骨形成和骨吸收增加,骨转换增加,去卵巢12w到18w骨量持续丢失,但较缓和,提示去卵巢后骨丢失在前4w最快更明显。因此,用于药物研究可选择去卵巢后4w时间进行。

Objective To study dynamic changes of the bone histomorphometric parameters at regular intervals in rats after OVX. Methods Seventy-two female rats aged 4.5 months were randomly divided into two groups according to the weight. Each group was subdivided into sham and OVX group. The mean weight was （256.3 ± 25.3） g. Tetracycline derivates and Calcein were administrated to each rat on two separate occasions to label sites of bone formation. Each group were sacrificed at 0,4 w, 12 w, 18 w. The undecalcified longitudinal proximal tibial metaphyseal sections were cut and stained for quantitative bone histomorphometriy. Results The cancellous bone volume was relatively stable in sham rats, but decreased in OVX rats at 4 w, 8 w, 12 w and 18 w after ovariectomy. The trabecular bone volume reduced at 4 w after ovariectomy, and then slowly decreased to a constant level from 8 w to 18 w, while the bone mass kept relatively stable;both bone formation and bone resorption increased markedly initially and then reduced slowly and bone turnover increased. The maximal significant increase occurred during the 4 w. Conclusions The bone mass at 4.5 M- 10 M in sham-rats keeps stable; but the trabecular bone volume in OVX rats decreases quickly during the first month（4 w）, and the initial rapid phase of bone loss is coincident with the maximal increase in bone turnover. At later times postovariectomy, trabecular bone mass appears to stabilize as bone turnover declines. These findings emphasize the close temporal relationship between increased bone turnover and the development of osteopenia in OVX rats .The postovariectomy-one-month rats can be chosen for study of the preventive effect of drugs on osteoporosis.