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中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (7): 721-727.doi: 10.12092/j.issn.1009-2501.2018.07.001

• 基础研究 •    下一篇

二氢杨梅素防治磨损颗粒诱导的小鼠颅骨骨溶解的实验研究

黄东辉1,郑杭生2   

  1. 1 杭州第三人民医院骨科,杭州 310009,浙江;2 浙江中医药大学药学院,杭州 310053,浙江
  • 收稿日期:2018-01-21 修回日期:2018-03-18 出版日期:2018-07-26 发布日期:2018-07-20
  • 通讯作者: 郑杭生,通信作者,男,博士,副教授,研究方向:中药活性成分及其新制剂的体内外研究。 Tel:0571-61768157 E-mail:hs-zheng@163.com
  • 作者简介:黄东辉,男,硕士,副主任医师,研究方向:关节创伤外科及骨质疏松骨折治疗。Tel:13136150807 E-mail:hzhdh1974o@163.com
  • 基金资助:

    国家自然科学基金(30873276)

Effects of dihydromyricetin on wear-particle-induced osteolysis in murine calvarial model

HUANG Donghui, ZHENG Hangsheng   

  1. Department of Orthopaedic Surgery, Hangzhou Third People's Hospital, Hangzhou 310009, Zhejiang, China
  • Received:2018-01-21 Revised:2018-03-18 Online:2018-07-26 Published:2018-07-20

摘要:

目的: 探讨二氢杨梅素(DMY)对磨损颗粒诱导的小鼠颅骨骨溶解的作用。方法: 选用30只8周龄雄性C57BL/J6小鼠,随机分成3组,每组10只。分别为假手术组(Sham)、阳性对照组(Control)和二氢杨梅素组(DMY)。假手术组手术不加钛颗粒,阳性对照组和DMY组手术时颅骨部位注入30 mg钛颗粒构建小鼠颅骨骨溶解模型。术后DMY组每天连续予500 mg/kg DMY灌胃;假手术组和阳性对照组给予相应体积的生理盐水灌胃。14 d后取眼眶静脉血,随后处死所有实验动物并收集颅骨标本。所有标本行Micro-CT扫描、采集计算机3D重建图像并进行定量分析,随后标本脱钙后以石蜡包埋,进行病理学分析。 结果: Micro-CT扫描3D重建图像显示DMY组小鼠颅骨表面骨溶解严重程度显著低于阳性对照组;Micro-CT扫描显示DMY组小鼠颅骨骨密度明显高于阳性对照组(P<0.05)。HE染色及TRAP染色分析显示,与阳性对照组相比,DMY组小鼠颅骨骨溶解区域破骨细胞数明显减少。DMY组小鼠血清IL-1β、TNF-α、NF-κB受体激活剂配体(RANKL)水平显著低于阳性对照组(P<0.05);骨保护素(OPG)水平显著高于阳性对照组(P<0.05)。体外细胞培养实验显示,DMY可在体外显著抑制RANKL诱导的破骨细胞分化。结论: DMY可有效抑制磨损颗粒诱导的小鼠颅骨骨溶解。

关键词: 小鼠, 二氢杨梅素, 钛颗粒, 破骨细胞, 骨溶解

Abstract:

AIM: To investigate the effects of dihydromyricetin (DMY) on wear-particle-induced osteolysis in murine calvarial model. METHODS: Thirty male C57BL/J6 mice were randomly divided into the sham group, the control group, and the DMY group (10 in each group). Except for the mice from the sham group, mice from the control group and DMY group received 30 mg Ti particles into calvaria to induce osteolysis in murine calvarial model. Mice from the DMY group were gavage-fed daily with DMY of 500 mg/kg, while mice from the sham group and control group were gavage-fed daily with saline. Calvaria and vein blood samples from each group were harvested for further micro-CT and pathological analysis at the 14th after the surgery. RESULTS:Micro-CT showed that the severity of osteolysis was significantly reduced in DMY group. And the BMD of the samples in DMY group was significantly higher than that of the control group(P<0.05). By the HE and TRAP staining analysis, less osteoclasts were found in the samples in DMY group. In addition, the application of DMY also decreased the serum TNF-α, IL-1β, and RANKL level yet improved OPG level as compared with the positive control group(P<0.05). DMY could significantly inhibit the differentiation of RANKL-induced osteoclast by in vitro cell culture experiments.CONCLUSION: DMY can inhibit the wear-particle-induced osteolysis in murine calvarial model.

Key words: mouse, dihydromyricetin, Ti particles, osteoclast, osteolysis

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