三种补肾中药有效成分对皮质酮致骨质疏松大鼠骨髓间充质干细胞基因表达谱的作用  

Effects of active ingredients in three kidney-tonifying Chinese herbal drugs on gene expression profile of bone marrow stromal cells from a rat model of corticosterone-induced osteoporosis

作　　者：卞琴[1,2,3,4] 黄建华[1,2] 杨铸[3,4] 宁友[1,2] 赵永见[3,4] 王拥军[3,4] 沈自尹[1,2] 

机构地区：[1]复旦大学中西医结合研究所 [2]复旦大学华山医院,上海2000402 [3]上海中医药大学脊柱病研究所 [4]上海中医药大学龙华医院,上海200032

出　　处：《中西医结合学报》2011年第2期179-185,共7页Journal of Chinese Integrative Medicine

基　　金：国家重点基础研究发展计划(973计划)(No.2010CB530402;2010CB530400)

摘　　要：目的:观察3种补肾中药淫羊藿、补骨脂和女贞子各自的有效成分淫羊藿苷、补骨脂素和齐墩果酸对皮质酮大鼠骨髓间充质干细胞(bone marrowstromal cell,BMSC)的调控作用。方法:50只Sprague-Dawley大鼠随机分为正常对照组、模型组、淫羊藿苷组、补骨脂素组、齐墩果酸组(后3组合称治疗组)。模型组和治疗组予皮质酮皮下注射,每日1次,连续14d。正常对照组予等剂量橄榄油皮下注射。治疗组皮质酮注射前5d开始按20mg/kg给予对应药物每日1次灌胃,连续19d。分别于造模第1、4、7、11和14天称量体质量,大鼠处死后取第4腰椎进行Micro-CT扫描,评价骨量改变情况。采用全骨髓贴壁培养法培养原代BMSC,于取材后第7天干细胞基因芯片技术检测mRNA表达。结果:造模和治疗后各组大鼠体质量没有发生明显变化。Micro-CT显示,皮质酮注射14d后,模型组与正常对照组之间,治疗组与模型组之间腰椎骨形态计量学参数未出现显著变化。干细胞基因表达谱显示在皮质酮改变的基因中,淫羊藿苷、补骨脂素和齐墩果酸分别可逆转11、12和15种基因。3个有效成分共同作用的基因有5种,涉及成骨分化、细胞周期调节、细胞代谢和Notch信号通路。结论:补肾中药可能从BMSC周期调节和细胞代谢等方面发挥促进BMSC成骨分化的作用,最终实现治疗骨质疏松的疗效,但其确切的机制还有待深入研究。Objective：To observe the effects of icariin,psoralen and oleanolic acid,the three active ingredients of Yinyanghuo（Herba Epimedii Brevicornus）,Buguzhi（Fructus Psoraleae）and Nuzhenzi（Fructus Ligustri Lucidi）,respectively,on gene expression profile of bone marrow stromal cells（BMSCs）from rats with corticosterone-induced osteoporosis.Methods：Fifty Sprague-Dawley rats were randomly divided into normal control group,untreated group,icariin group,psoralen group and oleanolic acid group（the last three groups are called treatment groups）.Rats in untreated group and treatment groups were subcutaneously injected with corticosterone once a day for 14 d while rats in normal control group were injected isodose of olive oil.Rats in the treatment groups were intragastrically administered with icarrin,or psoralen,or oleanolic acid at 20 mg/（kg·d）,respectively,5 d prior to modeling for 19 d.The body weight of rats was recorded on the 1st,4th,7th,11th,and 14th day after modeling,respectively.All rats were sacrificed and the fourth lumbar vertebrae were harvested for micro-CT scanning to evaluate bone mass.BMSCs were obtained ex vivo by the methods of bone marrow adherent culture.The mRNAs of BMSCs were detected by using gene chip technique on the 7th day of culture.Results：There was no significant difference in body weight of rats between untreated group and treatment groups.Micro-CT showed no significant difference in lumbar vertebral morphometry between the untreated and the normal control,or the untreated and treatment groups.In microarray,icariin,psoralen and oleanolic acid changed expressions of 11,12 and 15 genes compared to the normal level,respectively.These three active ingredients all acted on 5 genes involving osteoblast differentiation,cell cycle regulation,cell metabolism and Notch signal pathway.Conclusion：Traditional Chinese herbal drugs with the effect of tonifying the kidney may promote BMSCs to differentiate into osteoblasts by regulating BMSCs cycles and cell metabolism,and show

关 键 词：补肾药 淫羊藿苷 补骨脂素 齐墩果酸 间质干细胞 基因表达谱 动物实验 大鼠 

分 类 号：R285.5[医药卫生—中药学]