基于骨组织Dlx5启动子甲基化探究补肾中药复方对去卵巢骨质疏松症大鼠的疗效机制
The therapeutic mechanism of kidney-reinforcing traditional Chinese medicine compound on ovariectomized osteoporosis rats based on methylation of Dlx5 promoter in bone
  
DOI:10.3969/j.issn.1006-7108.2020.05.004
中文关键词:  绝经后骨质疏松症  补肾中药复方  Dlx5  甲基化  表观遗传
英文关键词:postmenopausal osteoporosis  kidney-reinforcing traditional Chinese medicine compound  distal-less homeobox 5  methylation  epigenetic
基金项目:辽宁省科学事业公益研究基金项目(GY-2018-0033)
作者单位
王剑1 刘剑辉1 李屹1 王实1 刘研1 丰雪妮1 刘永林1 刘文艳1 宋光熠1 郑洪新2* 1.辽宁省基础医学研究所辽宁 沈阳 110101 2.辽宁中医药大学辽宁 沈阳 110847 
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中文摘要:
      目的 基于骨组织Dlx5启动子甲基化水平,探索补肾中药复方对大鼠去卵巢骨质疏松症的疗效机制。方法 去卵巢建立绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)大鼠模型,分为正常组、模型组、补肾中药复方组、仙灵骨葆阳性对照组。灌胃14周后,X线吸收测量法检测骨密度,质谱法检测Dlx5启动子甲基化水平。结果 ①与正常组比较,模型组第1~6腰椎骨密度明显降低(P<0.01),骨组织Dlx5启动子-470bp~-4bp CpG2.3甲基化水平明显升高(P<0.01)。②与模型组比较,补肾中药复方组、仙灵骨葆阳性对照组第1~6腰椎骨密度明显升高(P<0.05),骨组织Dlx5 启动子-470bp~-4bp CpG1甲基化水平明显降低(P<0.05)。结论 补肾中药复方通过降低骨组织Dlx5启动子甲基化水平的表观遗传学机制,有效防治PMOP。
英文摘要:
      Objective To explore the therapeutic mechanism of kidney-reinforcing traditional Chinese medicine compound on ovariectomized osteoporosis rats based on methylation level of Dlx5 promoter in bone. Methods Postmenopausal osteoporosis (PMOP) rat model was established with ovariectomy. All the rats were divided into 4 groups: normal group, model group, kidney-reinforcing traditional Chinese medicine compound group, and Xianlinggubao positive control group. After 14 weeks of drug administration, bone mineral density was detected using X-ray absorptiometry. Dlx5 promoter methylation level was detected using MassARRAY. Results 1) Compared to those in normal group, bone mineral density of the lumbar vertebra 1-6 in model group decreased significantly (P<0.01), and the methylation level of Dlx5 promoter -470bp - -4bp CpG2.3 increased significantly in bone (P<0.01). 2) Bone mineral density of the lumbar vertebra 1-6 in kidney-reinforcing traditional Chinese medicine compound group and Xianlinggubao positive control group increased significantly (P<0.05), and the methylation level of Dlx5 promoter -470bp - -4bp CpG1 decreased significantly in bone (P<0.05), compared with those in model group. Conclusion Kidney-reinforcing traditional Chinese medicine compound prevents and interferes with PMOP effectively through the epigenetic mechanism of reducing Dlx5 promoter methylation level in bone.
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