摘要
目的研究骨靶向雌激素大黄酸-雌酮(LC)对去卵巢大鼠骨组织中的ERα和ERβmRNA表达的影响。方法 72只6月龄雌性未孕Wistar大鼠,分为6组:假手术组(Sham)、去卵巢模型组(OVX)、雌酚酮组(E,OVX+雌酚酮1.0 mg/kg·d)、大黄酸-雌酮高(H-LC,OVX+LC 1.0 mg/kg·d)、中(M-LC,OVX+LC 0.5 mg/kg·d)、低(L-LC,OVX+LC 0.25 mg/kg·d)剂量组,除假手术组外其余各组均行双侧卵巢切除。给药24周后,采用放射免疫方法测定血中雌二醇水平,采用RT-PCR法测定子宫及骨组织ERα和ERβmRNA水平。结果与Sham组比较,OVX组雌二醇水平明显降低,与OVX组比较,E组和H-LC、M-LC组大鼠血清雌二醇明显升高,L-LC组与OVX组无明显差别。Sham组胫骨近端ERαmRNA和ERβmRNA均有表达,OVX组ERβmRNA表达水平与Sham组相比降低,未检出ERαmRNA。E组ERαmRNA和ERβmRNA水平均与Sham组无差异,大黄酸-雌酮各组均未检出ERαmRNA,ERβmRNA相对表达量高于OVX组,大黄酸-雌酮各剂量组之间ERβmRNA无明显差异。Sham组大鼠子宫组织有ERαmRNA和ERβmRNA表达,OVX组ERαmRNA表达量明显降低,未检出ERβmRNA。E组大鼠子宫组织ERαmRNA和ERβmRNA均较OVX组上调。大黄酸-雌酮各剂量组之间ERαmRNA无明显差异,但均低于E和Sham组。结论大黄酸-雌酮在骨及子宫均能选择性上调ERβmRNA表达,而对ERαmRNA无影响,雌酚酮对两种亚型无选择性,这可能是大黄酸-雌酮对骨具有保护作用而对子宫并无雌激素样刺激作用的原因之一。
Objective To investigate the effect of the bone-targeted estrogen, rhein-estrone （LC）, on the expression of ERa and ERβ mRNA in the bone and uterine in ovariectomized rats. Methods Seventy-two 6-month Wistar female rats were randomly divided into 6 groups ： Sham group （Sham） , ovariectomized rat model group （OVX） , estrone group （E, OVX ＋ estrone 1.0 mg/ kg.d）, H-LC group （OVX ＋ rhein-estrone 1.0 mg/kg.d）, M-LC group （OVX ＋ rhein-estrone 0. 5 mg/kg.d）, and L-LC group （OVX ＋ rhein-estrone 0. 25 mg/kg.d）. Rats in all the groups except those in Sham group were bilaterally ovariectomized. After 24-week administration, the serum level of estradiol was detected using radioimmunoassay. The expression of ER a and ERA3 mRNA in bone and uterine was detected using reverse transcription polymerase chain reaction assay （RT-PCR）. Results Compared with that in Sham group, the serum level of estradiol in OVX group decreased significantly. When compared with that in OVX group, the serum level of estradiol increased significantly in E group, H-LC group, and M-LC group except in L-LC group. The expression of ERa mRNA and ERβ mRNA in the proximal tibia of rats in Sham group was identified. The expression of ERβ mRNA in OVX group was lower than that in Sham group, while no expression of ERa mRNA in OVX group was observed. The expression of ERa and ERβ mRNA in E group showed no significant difference with that in Sham group. Compared with that in OVX group, the expression of ERβ mRNA was up-regulated in all 3 rhein-estrone groups, but no expression of ERct mRNA was observed. No significant difference of the expression of ERβ mRNA was observed among the rhein-estrone groups. The expression of ERa and ERβ mRNA in the uterine was identified in Sham group. The expression of ERa mRNA in OVX group was lower than that in Sham group, while no expression of ERβ mRNA in OVX group was observed. The expression of ERa and ERβ mRNA in the uterine of rats in E group increased compared with that in OVX group. No significant difference of ERa mRNA expression was observed among the rhein-estrone groups, while a down-regulated expression of ERa mRNA was observed in all rhein-estrone groups when compared with that in Sham group and E group. Conclusion Rhein-estrone can selectively up-regulate the expression of ERβ mRNA in the bone and the uterine, but show no effect on the expression of ERct mRNA. Estrone has no selectivity of both subtypes. This is a possible reason that rhein-estrone has protective effect on the bone, but shows no estrogen-like effect on the uterine in ovariectomized rats.
出处
《中国骨质疏松杂志》
CAS
CSCD
北大核心
2013年第12期1241-1245,共5页
Chinese Journal of Osteoporosis
基金
中国博士后科学基金面上项目(20084441177)
