铁过载对去势大鼠骨代谢的影响

目的 观察去势骨质疏松模型大鼠在铁过载状况下骨转换和骨密度变化,探讨铁过载与绝经后骨质疏松症的相关作用.方法 将32只3月龄雌性SD大鼠按完全随机法平分为假手术组（Sham组）、去势组（OVX组）、去势基础上2种剂量枸橼酸铁铵组（FAC）干预组,即低剂量枸橼酸铁铵干预组（FAC1组）、高剂量枸橼酸铁按干预组（FAC2组）.大鼠行双侧卵巢切除术,去势后1周分别用枸橼酸铁铵90（FAC1）和180 mg/kg（FAC2）腹腔注射,每周2次,共9周,OVX组和 Sham组按同样方式和频次注射等量生理盐水.9周后心脏取血,检测血清铁、β-Ⅰ型胶原羧基端肽（β-CTX）、骨钙素（BGP）含量.用肝脏Perl＇s法铁染色,用原子吸收法检测胫骨铁含量,观察股骨病理改变,并对股骨远端Micro-CT行三维分析.结果 与Sham组比较,OVX组去势后血清铁含量、肝脏普鲁士蓝铁染色差异无统计学意义,但胫骨铁含量显著下降;与Sham组、OVX组比较,FAC1组、FAC2组血清铁、胫骨铁含量升高,肝脏蓝染铁颗粒显著增加,差异有统计学意义（P＜0.05）.与Sham组比较,OVX组β-CTX、BGP高于Sham组（P＜0.05）,FAC1和FAC2组较OVX组β-CTX增高（P＜0.05）;但BGP水平在3组间差异无统计学意义.病理组织形态学结果显示,与OVX组比较,铁干预组骨小梁形态结构稀疏,间距增大.Micro-CT分析表明,与OVX组比较,去势后铁干预组骨密度（BMD）、骨小梁厚度（Tb.th）、骨体积分数（BV/TV）、骨小梁数量（Tb.N）均显著下降（均P＜0.05）,骨小梁分离度（Tb.Sp）、结构模型指数（SMI）、各向异性度（DA）显著升高（均P＜0.05）.结论 大鼠去势后合并铁过载促进骨吸收,使骨小梁结构进一步稀疏,骨质密度进一步降低.

Iron overload exacerbaked osteoporosis in ovariectomized rats

Objective We use ovarieteeted rats to imitate postmenopausal osteoporosis, and the iron overload conditions were established by the intraperitoneal injection of ferric ammonium citrate （FAC） as iron donor. We then ex- plore the effect of iron overload on bone metabolism under postmenopausal conditions. Methods 32 three-month-old fe- male SD rats were randomly divided into 4 groups （n = 8 for each group） ： Sham group, OVX group and two iron over-load groups, FAC1 and FAC2 group, which were intervened by FAC. One week after the operation, all groups were es- tablished by the intraperitoneal injection of normal saline and FAC, twice per week. Three months later, serum fi＇ee iron concentration, estrogen, ~-CTX, BGP levels were measured in peripheral blood. The iron content of the tibia was meas- ured by ICP tester. The iron particle in the liver was observed by Perls＇ Prussian-blue method. The trabecular architectur- al changes of the right femur were observed by histomorphology. A high resolution micro-CT was used to scan the left fe- mur, and mircro-architeeture parameters were analysed. Results The serum E2 were lowered in OVX group and FAC groups than in Sham group （ P 〈 0. 05 ）. There was no significant difference between the Sham group and the OVX group in serum ti＇ee iron content and Perls＇ staining of the liver, while the tibia iron content in OVX group was lower than the Sham group （ P 〈 0. 05 ）. The FAC groups showed significant higher serum iron and tibia iron content, and obvious blue iron particles. Both [3-CTX and BGP increased significantly in OVX group than the Sham group （P 〈 0. 05 ）. Compared with the OVX group, [3-CTX rather than BGP increased significantly in FACI group and FAC2 group. The morphology of trabecular in FAC1 and FAC2 is further deteriorated than the OVX group. Compared with the OVX group, the mierotomo- graph reconstruction analysis showed the BV/TV, Tb. N, Tb. th and BMD in FAC groups decreased significantly （P 〈 0. 05） , while the Tb. Sp, SMI, DA were significantly higher （P 〈0.05）. Conclusion Iron overload could exacert）ate post-menopausal osteoporosis, which might be through the pathological mechanism of enhancing bone resorption. This study provide the experimental data for the effect of iron overload on postmenopausal osteoporosis, which will enrich the concept of the pathological mechanism of this disease.