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| 替格瑞洛促进Ⅰ型成骨不全小鼠骨形成的治疗研究 |
| The therapeutic effect of Ticagrelor of the promotion of bone formation in osteogenisis imperfecta type I mice |
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| DOI：10.3969/j.issn.1006-7108.2023.11.003 |
| 中文关键词: 成骨不全症 替格瑞洛 破骨细胞 小鼠 |
| 英文关键词:osteogenisis imperfecta Ticagrelor osteoclast rat |
| 基金项目:国家重点研发计划（2017YFC1001904）；国家自然科学基金面上项目（82272447） |
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| 中文摘要: |
| 目的 探索替格瑞洛（Ticagrelor）促进Ⅰ型成骨不全小鼠（Col1a1+/-365）骨形成的效果及作用机制。方法 选取6只8周龄野生C57/BL小鼠作为正常对照组（WT），选取12只8周龄Col1a1+/-365小鼠，随机分为DMSO对照组和替格瑞洛治疗组，每组6只，通过灌胃给药[2 mg/(kg?d)]进行治疗，DMSO对照组每天灌胃同等剂量DMSO。10周后分离各组小鼠的股骨，通过Micro-CT检测股骨骨体积分数（BV/TV）、骨小梁数量（Tb.N）、骨小梁厚度（Tb.Th）、骨小梁模式因子（Tb.Pf）等参数的变化；采用HE染色检测股骨形态学变化；采用Trap染色检测破骨细胞的数量变化；采用Real-time PCR法检测股骨破骨特异基因Mmp9、Ctsk、Nfatc1的表达情况。结果 ①与DMSO对照组比较，Ticagrelor治疗组BV/TV、Tb.N、Tb.Th和骨面积（B.Ar）均增高（P＜0.05），而Tb.Pf降低（P＜0.05）。Ticagrelor治疗组小鼠与WT组小鼠BV/TV、Tb.N和Tb.Th差异无统计学意义（P＞0.05）；②与DMSO对照组比较，Ticagrelor治疗组破骨细胞数量减少（P＜0.05），破骨特异基因Mmp9、Nfatc1表达水平降低（P＜0.05）。结论 替格瑞洛可以有效改善Col1a1+/-365小鼠的股骨微观结构，促进骨形成，其机制可能与抑制破骨细胞分化相关。 |
| 英文摘要: |
| Objective To explore the effect of Ticagrelor on osteogenisis imperfecta (OI) type I mice. Methods Six 8-week-old wild-type male mice served as the WT group. Twelve 8-week-old Col1a1+/-365 mice that mimic OI type I were randomly divided into DMSO control group and Ticagrelor treatment group (n=6). Mice in the treatment group received 2 mg/(kg?d) Ticagrelor once per day by gavage for 10 weeks. Mice in the DMSO control group received equal corn oil containing equal DMSO. Murine femurs were collected at the end of the treatment to evaluate the therapeutic effect. Bone microstructure-related indexes including bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular bone pattern factor (Tb.Pf) were detected with micro-CT. The femoral morphological manifestations were measured using HE staining. The number of osteoclasts were determined with TRAP staining. The expression of matrix metalloproteinase 9 (MMP9), cathepsin K (Ctsk), and nuclear factor of activated T cells c1 (Nfatc1) of femurs was detected with real-time PCR. Results Compared with the DMSO control group, Col1a1+/-365 mice treated with Ticagrelor showed increased BV/TV, Tb.N, Tb.Th, and bone area (B.Ar, P<0.05) but decreased Tb.Pf (P<0.05). Ticagrelor treated Col1a1+/-365 mice had less number of osteoclasts and lower expression of MMP9 and Nfatc1 than those in DMSO control group (P<0.05). Conclusion Ticagrelor treatment significantly improves femoral microstructure and promotes bone formation of Col1a1+/-365 mice partly by inhibiting osteoclast differentiation. |
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