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| 雷帕霉素延缓老年小鼠脊柱退变的实验研究 |
| Rapamycin delays spine degeneration in aged mice |
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| DOI：10.3969/j.issn.1006.7108.2017.12.006 |
| 中文关键词: mTOR信号通路 脊柱 椎间盘 退变 雷帕霉素 |
| 英文关键词:mTOR signaling pathway Spine Intervertebral disc Degeneration Rapamycin |
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| 中文摘要: |
| 目的 探讨雷帕霉素(Rap)对老年小鼠自发性脊柱退变的保护作用。方法 将20只老年C57B6小鼠（27月龄）随机分为实验（30m+Rap）和对照（30m）两组，实验组小鼠每天灌胃1次西罗莫司(2mg/(kg?d))，对照组灌等量生理盐水，均持续灌胃3个月后取材，通过μCT观察椎体结构和进行骨小梁分析，组织切片行HE和阿尔新蓝染色观察椎体和椎间盘情况，还进行TRAP染色检测破骨细胞数目和免疫组织检测二型胶原（COLⅡ）表达及分布。结果Micro-CT检查测量，发现雷帕霉素能缓解脊柱椎体骨皮质变薄和骨小梁减少，主要表现在喂雷帕霉素后椎体的BV/TV及骨小梁数量增加，骨小梁分离度减少，但骨小梁厚度无明显改变。HE染色和阿尔新蓝染色显示雷帕霉素能缓解老年小鼠椎间盘退变，表现在30m+Rap组小鼠椎体骨小梁较30m组多，30m+Rap组小鼠椎间隙较30m组大，30m组纤维环结构紊乱，向髓核内生长替代部分髓核组织，生长板和软骨终板软骨退变明显。TRAP染色检测，发现30m+Rap组破骨细胞减少，免疫组化检测显示COLⅡ在30m组小鼠的软骨终板和生长板表达明显较30m+Rap组减少。结论 雷帕霉素能通过mTORC1调控破骨细胞和软骨细胞，延缓老年小鼠脊柱退行性病变。 |
| 英文摘要: |
| Objective To study the protection effect of rapamycin on spontaneous spinal degeneration in aged mice. Methods Twenty aged C57B6 mice (27 months) were divided into experimental group (30m+Rap) and control group (30m). Mice in the experimental group were lavaged with sirolimus (2 mg/kg/d), and mice in the control were filled with saline. After 3 months of continuous lavaging, Micro-CT and tissue slice staining were used to observe vertebrae and intervertebral discs and for the analysis of trabeculae. TRAP staining detection of osteoclasts and immunohistochemical detection of type II collagen (COL Ⅱ) expression were conducted. Result Micro-CT detection found that rapamycin could alleviate the thinning of cortical bone and the decrease of trabeculae of vertebral body, mainly showing as an increase in BV/TV and number of trabeculae and reduced degree of trabeculae separation, but the thickness of trabeculae had no obvious changes. HE staining and alcian blue staining showed that the number of vertebral trabeculae in mice in the 30 m + Rap group was greater than that of the 30 m group, consistent with the results of Micro-CT. The intervertebral space of the 30 m + Rap group mice was greater; the fiber ring structure of the 30 m group was in disorder, with the fiber grew into nucleus pulposus and replaced part of nucleus pulposus tissue. Growth plate and cartilage endplate cartilage degenerated obviously in the 30 m group. TRAP and COLⅡ immunohistochemical staining found that osteoclasts decreased obviously in KO mice and COLⅡ expression in growth plate and cartilage endplate in the 30 m + Rap group was higher than that in the 30 m group. Conclusion Rapamycin could regulate chondrocytes and osteoclasts to delay spine degenerative diseases in aged mice through mTORC1 signaling pathway. |
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