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

作　　者：王剑[1] 刘剑辉 李屹[1] 王实[1] 刘研 丰雪妮 刘永林[1] 刘文艳[1] 宋光熠[1] 郑洪新[2] WANG Jian;LIU Jianhui;LI Yi;WANG Shi;LIU Yan;FENG Xueni;LIU Yonglin;LIU Wenyan;SONG Guangyi;ZHENG Hongxin(Liaoning Institute of Basic Medicine, Shenyang 110101;Liaoning University of Traditional Chinese Medicine, Shenyang 110847, China)

机构地区：[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

出　　处：《中国骨质疏松杂志》2020年第5期640-645,共6页Chinese Journal of Osteoporosis

基　　金：辽宁省科学事业公益研究基金项目(GY-2018-0033)。

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-470 bp^-4 bp 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-470 bp^-4 bp 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。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-470 bp--4 bp 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-470 bp--4 bp 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.

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 

分 类 号：R965[医药卫生—药理学] R-332[医药卫生—药学]