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| 异补骨脂素对去卵巢骨质疏松小鼠骨髓间充质干细胞作用机制研究 |
| The effects of isopsoralen on bone marrow mesenchymal stem cells of mice with ovariectomized osteoporosis and the relevant mechanisms |
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| DOI：10.3969/j.issn.1006.7108.2016.08.009 |
| 中文关键词: 异补骨脂素 骨髓间充质干细胞 骨质疏松 小鼠 |
| 英文关键词:Isopsoralen Bone mesenchymal stem cells Osteoporosis Mice |
| 基金项目:国家自然科学基金（81560368)；内蒙古自治区人民医院院内基金（201428)；内蒙古自治区人民医院博士科研启动资金 (CBS201532) |
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| 中文摘要: |
| 目的 探讨异补骨脂素对去卵巢骨质疏松小鼠骨髓间充质干细胞（bone mesenehymal stem cells，BMSCs)作用机制。方法 18只C57/BL6雌鼠随机平均分为假手术组（Sham)、去卵巢组（OVX)和去卵巢加异补骨脂素组（OVX + ISO),各组6只。OVX组和OVX +ISO组分离背部近髂脊处肌肉，取出双侧卵巢，结扎上部输卵管，剪去双侧输卵管。Sham组相同人路后剪去包裹卵巢周围的部分脂肪组织。OVX +ISO组在去卵巢前5天开始灌胃异补骨脂素，灌胃剂量为20 mg/(kg?d)，灌胃持续时间2个月，Sham组以等剂量生理盐水灌胃。造模后12周处死小鼠，取股骨下段评价骨髓腔中脂肪细胞量，行micro-CT扫描评价股骨下段骨量改变及RUNX2、PPAR-γ免疫荧光检测。结果 异补骨脂素能明显减少由于去卵巢引起的股骨下段脂肪细胞增多；与此同时，异补骨脂素治疗能明显改善由于去卵巢引起的股骨下段骨量丢失，即OVX+ISO组骨小梁厚度（Tb. Th)、骨体积/总体积（BV/TV)、骨小梁数量（Tb.N)大于OVX组，差异具有统计学意义（P<0. 05);而OVX + ISO组骨小梁体积（Tb. Sp)小于OVX组，差异具有统计学意义（P <0.05)。对去卵巢C57/BL6小鼠股骨下段进行RUNX2和PPAR-γ免疫荧光提示，异补骨脂素治疗能增加股骨下段由于去卵巢引起的RUNX2表达降低，同时能抑制PPAR-γ表达增加，即OVX + ISO组股骨下 段RUNX2、PPAR-γ免疫荧光表达强度高于OVX组，差异具有统计学意义（P < 0. 05)。结论 异补骨脂素对去卵巢小鼠BMSCs的作用机制为治疗骨质疏松提供了新的临床治疗手段。 |
| 英文摘要: |
| Objective To study the effects of isopsoralen on bone marrow mesenchymal stem cells (BMSCs) of mice with ovariectomized osteoporosis and to explore the relevant mechanisms. Methods Eighteen C57/BL6 female rats were randomly divided into sham operation group (sham), ovariectomized group (OVX) and ovariectomized plus isopsoralen group (OVX + ISO) , with 6 rats in each group. In the OVX group and OVX + ISO group, surgery was performed from the back of the proximal iliac spine muscle, and bilateral ovaries were removed and the bilateral fallopian tubes cut off after the ligation of the upper fallopian tube. In the Sham group, part of the fat tissue around the ovary was removed after the same procedure. All rats of the OVX + ISO group was gavaged isopsoralen at a dose of 20 mg/( kg?d) for two months began 5 days before the removal of ovaries. All of the rats in the sham group were gavaged with equal dose of normal saline. After 12 weeks, rats were sacrificed to evaluate the quality of fat cells in the bone marrow cavity. Bone mass of femur was evaluated by micro-CT scan and RUNX2 and PPAR-γ were also assessed. Results Isopsoralen can significantly decrease the increase in fat cells resulted from ovariectomized in OVX mice. In addition, isopsoralen treatment can significantly reduce the loss of bone mass due to ovariectomized in the lower femur. Trabecular bone thickness (TB. Th)，bone volume / total volume (BV/TV) and trabecular number (TB. N) were all significant greater (P <0. 05) in the OVX + ISO group than those in the OVX group； and bone trabecular separation (TB. SP) was significant lower (P < 0. 05) in the OVX + ISO group than that in the OVX group. The Runx2 and PPAR-γ immune fluorescence tips in the lower femur of C57/BL6 mice showed that isopsoralen treatment could increase Runx2 expression that was decreased due to ovariectomy, and inhibit increased expression of PPAR-γ, namely the immune fluorescence expression intensities of Runx2 and PPAR-γ in lower femur were significant higher in the OVX + ISO group than that of OVX group (P < 0. 05). Conclusion Study the effects and mechanisms of isopsoralen treatment on BMSCs in ovariectomized mice provides a new avenue for the treatment of osteoporosis. |
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