雌激素对去势骨质疏松症大鼠骨密度和骨代谢影响的实验研究

摘要

目的 研究雌激素对去势骨质疏松症模型大鼠骨密度(bone mineral density,BMD)和骨代谢的影响,并探讨其治疗骨质疏松症的机制.方法 将48只雌性SD大鼠随机分配成对照组、模型组、雌激素组和雌激素+三苯氧胺组,每组12只.除对照组外,其他各组大鼠采用双侧卵巢摘除法制备骨质疏松症模型.雌激素组给予尼尔雌醇(1 mg/kg)灌胃,1 次/周;雌激素+三苯氧胺组给予尼尔雌醇(1 mg/kg)和三苯氧胺(3 mg/kg)灌胃,1次/周;对照组和模型组分别使用等量生理盐水灌胃,均持续3个月. 3个月后取材,检测大鼠左侧股骨BMD和股骨骨矿物盐含量、血清钙含量以及胫骨中骨骼钙含量;酶联免疫法检测大鼠血清碱性磷酸酶(alkaline phosphates,ALP)、血清抗酒石酸酸性磷酸酶-5b(tartrate resistant acid phosphatase-5b, TRAP-5b)的含量;免疫组化检测大鼠胫骨中骨保护素(osteoprotegerin,OPG)和核因子κB受体活化因子配体(receptor activator for nuclear factor-κB ligand,RANKL)蛋白的表达情况.结果 治疗前,与对照组比较其他各组血清钙含量和血清TRAP-5b含量均显著升高(P＜0.05),骨钙含量、BMD和骨矿物盐含量显著降低(P＜0.05),血清ALP含量无显著性变化(P＞0.05);治疗后,与模型组比较雌激素组血清钙含量、血清TRAP-5b含量以及胫骨组织RANKL蛋白表达均显著降低(P＜0.05),骨钙含量、血清ALP含量、BMD、骨矿物盐含量以及胫骨组织OPG蛋白表达均显著升高(P＜0.05),而治疗后,与模型组比较雌激素+三苯氧胺组各项指标变化差异无统计学意义(P＞0.05).结论 雌激素通过显著性提高去卵巢骨质疏松模型大鼠骨骼钙、ALP、股骨骨密度、骨矿物盐以及OPG的含量,抑制骨钙流失、TRAP-5b及RANKL蛋白表达,达到改善骨质疏松的作用.%Objective To study the effect of estrogen on bone mineral density and bone metabolism in osteoporotic rats. Methods 48 female SD rats were randomly divided into control group (sham operation group), model group, estrogen group and estrogen combined with tamoxifen group, with 12 in each group.All groups were ovariectomized except for the control group.Rats in the estrogen group were given nilestriol (1 mg/kg) once per week, rats in the estrogen combined with tamoxifen group were given nilestriol (1 mg/kg) and tamoxifen (3 mg/kg) once per week, and the model and control groups were given the same amount of saline lavage.After 3 months, bone mineral density (BMD) and content of bone mineral salt of the left femur, serum calcium and tibia bone calcium were assessed.ALP and TRAP-5b levels were detected using ELISA method .Protein expression levels of OPG and RANKL were measured using IHC-P method.Results Before therapy, serum calcium and the level of TRAP-5b in the model group, estrogen group and estrogen combined with tamoxifen group were significantly higher than that in the control group (P＜0.05), and bone calcium, BMD and the content of bone mineral salt were significantly lower (P＜0.05), while the serum content of ALP was not significantly different (P ＞0.05).After treatment, the levels of serum calcium, TRAP-5b and RANKL expression in the estrogen group were significantly decreased compared with the model group (P＜0.05), and the level of bone calcium, ALP, OPG, BMD and the content of bone mineral salt were significantly higher in the estrogen group compared with the model group (P＜0.05).However, after therapy, there were no significant differences between the estrogen combined with tamoxifen group and the model group.Conclusion Estrogen can treat osteoporosis by significantly improving bone mass and inhibiting osteoclast activities.