选择性雌激素受体调节剂雷洛昔芬阻止去卵巢大鼠骨丢失的机制

Prevention of bone loss by selective estrogen receptor modulators: raloxifene in the ovariectomized rat

目的 了解选择性雌激素受体调节剂雷洛昔芬 (RLX)阻止去卵巢大鼠骨丢失的机制。对骨质疏松症模型大鼠进行雌激素及选择性雌激素受体调节剂类药物RLX治疗 ,观察其对去卵巢大鼠骨组织光镜、电镜及骨密度 (BMD)等各种指标的影响。 方法 用 3月龄雌性SD大鼠 32只 ,随机分为卵巢未切除组、卵巢切除组、雌激素治疗组、RLX治疗组 ,5个月后处死 ,检测股骨、腰椎及全身BMD、子宫重量、骨形态。 结果 卵巢切除组经RLX治疗 3个月后腰椎、股骨、全身BMD增加35 %、4 0 %、2 1% ,分别为 (0 2 5 6± 0 0 2 2 ) g/cm2 、(0 2 93± 0 0 15 ) g/cm2 和 (0 36 8± 0 0 2 5 ) g/cm2 ;RLX组大鼠骨小梁表面的破骨细胞数比卵巢切除组减少 ;与卵巢切除组相比 ,雌激素治疗组的子宫重量增加了 5 5 % ,而RLX组则对子宫无明显刺激作用。 结论 RLX及雌激素都具有防治骨质疏松的作用 ,RLX能阻止去卵巢所造成的骨丢失。

Objective Bone loss due to estrogen deficiency can be prevented by estrogen replacement therapy. But it produces a number of side effects associated with the cancer of breast and uterus which limits its application. Selective estrogen receptor modulators(SERMs) are a new category of therapeutic agents, they could bind to estrogen receptors with high affinity and mimic the effects of estrogen in some tissue but act as estrogen antagonists in others. This study was designed to observe the effect of Raloxifene on osteoporosis of the OVX rat model and probe into its mechanism. Methods Thirty-two 3-month-old female SD rats were randomly divided into four groups: the basal control, the OVX, OVX with RLX,OVX with DES. All rats were killed at the end of the experiment five months later. Body weight, bone mineral density (BMD), bone histomorphometry, uterine weight were measured. Results BMD of total body, lumbar spine and femur in OVX rats was significantly lower than that of rats treated with RLX by decreasing 21%, 35%, 40%, respectively. The number of osteoclast was significantly decreased in RLX-treated-OVX rats compared to OVX rats (P<0.05). RLX treatment prevented OVX-induced bone loss. In the rats given DES treatment, the uterine weight increased by 55% while RLX had no effect on uterine weight(P<0.05) compared with OVX rats. Conclusions Both DES and RLX are effective on preventing bone loss in OVX rats , but the data suggest that RLX may be a significant alternative to DES for the prevention and the treatment of postmenopausal osteoporosis.