雌马酚对去卵巢后大鼠骨质疏松症的影响

Equol improves osteoporosis in ovarietomized rats

目的观察雌马酚对去卵巢后大鼠骨质疏松症的作用。方法雌性SD大鼠去卵巢以建立骨质疏松症模型。健康3月龄雌性SD大鼠分为5组:假手术组(sham)、去卵巢组(ovarietomized,OVX)、OVX+雌马酚高剂量组[equol,Eq,0.5 mg/(kg·d)]、OVX+雌马酚低剂量组[equol,Eq,0.25 mg/(kg·d)]、OVX+雌二醇阳性对照组(estradiol,E2)。去卵巢8周后,按以上分组继续给药8周后取右侧股骨检测骨密度(bone mineral density,BMD),眼部取血检测血钙、血磷和骨钙素(bone gla protein,BGP)含量;ELISA检测血清雌激素(estrogen,ES)、成骨细胞护骨素(osteoprotegerin,OPG),破骨细胞分化因子(receptor activator of nuclear factor kappa B ligand,RANKL)水平;qRT-PCR法检测OPG和RANKL mRNA的表达。结果 OVX组与sham组比较,ES值、BMD和血钙水平显著下降(P<0.05),分别为sham组的78.1%、84.4%和83.2%。同时,OVX组大鼠血磷和BGP含量明显升高(P<0.05),表明去卵巢后骨质疏松症模型造模成功;OVX组大鼠与sham组比较,OPG蛋白和OPG mRNA表达量显著下降,RANKL蛋白和RANKL mRNA表达量明显升高(P<0.05),而Eq和E2组处理后能显著增加OPG蛋白和OPG mRNA表达,下调RANKL蛋白和RANKL mRNA表达,同时提高OVX大鼠的BMD和血钙水平,降低血磷和BGP含量(P<0.05)。结论雌马酚能有效改善去卵巢后大鼠骨质疏松症,可能与其能上调OPG而抑制RANKL分泌有关。

Objective To determine the effect of equol（ Eq） on osteoporosis in ovarietomized rats.Methods Ovariectomized female SD rats were employed to establish a model of osteoporosis. Three-monthold healthy female SD rats were randomly divided into 5 groups,that is,sham-operation group（ sham）,ovariectomized group（ OVX）,OVX and high-dose of Eq [0. 5 mg /（ kg·d） ] group,OVX and low-dose of Eq [0. 25 mg /（ kg · d） ] group, OVX ＋ estradiol（ E2） positive control group. In 8 weeks after ovariectomization,all rats were treated as described above through intraperitoneal injection for another 8weeks. The bone mineral density（ BMD）,blood calcium,phosphorus and osteocalcin content were detected.Moreover,the levels of serum estrogen（ ES）,osteoprotegerin（ OPG）,and receptor activator of nuclear factor kappa B ligand（ RANKL） were measured by ELISA. The expression of OPG and RANKL at mRNA level were determined by qRT-PCR. Results Compared with the sham group,the levels of ES,BMD and serum calcium were significantly decreased（ P〈0. 05） in the OVX group,respectively,which were 78. 1%,84. 4% and 83. 2% of sham group,respectively. Meanwhile,the levels of serum phosphorus and bone gla protein（ BGP） in OVX group were notably increased（ P〈0. 05） compared to the sham group,indicating the osteoporosis model was successful. Eq and E2 markedly induced the mRNA and protein expression of OPG and inhibited RANKL protein and mRNA expression,and thereby,enhanced the levels of BMD and serum calcium,and reduced the content of serum phosphorus and BGP in OVX rats（ P〈0. 05）. Conclusion Eq could improve osteoporosis in ovariectomized rats possibly through enhancing OPG secretion and inhibiting RANKL secretion.