淫羊藿黄酮类成分预防去势大鼠骨质疏松的作用机制

目的 研究中药淫羊藿的黄酮类成分(FE)预防绝经后骨质疏松的作用是否通过促进肠钙吸收途径.方法 12月龄雌性Wistar大鼠45只,随机分为假手术组和卵巢切除组,即OVX组(卵巢切除+溶媒)、FE组(卵巢切除+淫羊藿黄酮类成分)、CS组(卵巢切除+钙剂+溶媒)和FE+CS组(卵巢切除+淫羊藿黄酮类成分+钙剂).卵巢切除4 d后,给药组开始灌喂,FE和(或)CS,连续用药12周.处死动物留取尿液和血清分别测定肠钙吸收指标,钙代谢自稳调节激素和骨转换标志物.截取左侧股骨近端,分别测定骨强度、骨材料-结构参数(包括肢体定量CT测定的体积骨密度、骨截面分布和显微CT定量测定的骨小梁三维结构)以及肢体定量CT定义的骨表面参数.结果 FE能显著预防大鼠去势引起的骨强度和材料结构的退化,对去势后子宫重量的改变没有影响,OVX组为(572±23)g,FE组为564 g,P＞0.05.钙剂(CS组)不能预防去势导致的骨强度的下降.FE和CS之间的析因分析结果表明两者联合应用能够分别在促进肠钙吸收和抑制骨吸收方面产生协同增强作用,但在抑制甲状旁腺激素方面没有协同效应;FE和CS在骨形成参数和骨材料-结构-强度参数方面也并没有体现协同增强作用.结论 中药淫羊霍的黄酮类成分能有效地预防去势大鼠骨质疏松,且不刺激子宫增生,其抑制骨吸收和促进骨形成的作用机制并非依赖肠钙吸收途径.

Epimedium-derived flavonoids prevent ovariectomy-induced osteoporosis in rats independent of its enhancement in intestinal calcium absorption

Objective To test our hypothesis whether a group of flavonoids (FE) derived from herbal Epimedium exerted its prevention of estrogen-deficiency-induced osteoporosis mainly through an enhancement in intestinal calcium absorption. Methods Forty-five 12-month-old female Wistar rats were randomly assigned into one sham-operated group and four ovariectomy (OVX) subgroups, i.e. OVX with vehicle (OVX group), OVX with FE (FE group), OVX with calcium supplement (CS group), and OVX with FE and CS. Daily oral administration of FE (10 mg·kg-1·d-1) and/or CS (56 mg·kg-1·d-1)started on day 4 after OVX for 12 weeks. Before sacrificing the animals, urine and serum samples were collected for assaying indicators for intestinal calcium absorption, regulator of calcium homeostasis and markers for bone turnover. Then, the left proximal femur was dissected for the primary-end-point index(failure force) , and the second-end-point indexes (pQCT-calculated densitometry, geometry and micro-CT-quantified 3-D trabecula mictroarchitecture), as well as pQCT-defined cross-sectional envelope. Results FE prevented OVX-induced deterioration in failure force as well as the second-end-point indexes with no increase in uterus weight. CS had no prevention effect on OVX-induced reduction in failure force. Two-way factorial interaction analysis between FE and CS showed that the un-enhanced suppression of parathyroid hormone for calcium homeostasis provided no link between the enhanced intestinal calcium absorption and the enhanced inhibition of bone resorption in the present study. Furthermore, discrepancy between the enhanced intestinal calcium absorption and the un-enhanced primary / second-end-point indexes as well as anabolic effect was also found by the interaction analysis. Conclusion Independent of intestinal calcium absorption,FE inhibited bone resorption, stimulated bone formation and accordingly prevented osteoporosis without hyperplastic effect on uterus in the OVX rat model.