左归丸与雌二醇调控去卵巢大鼠骨髓间充质干细胞多时相基因表达谱改变的比较研究  

Comparison of Temporal Gene Expression Patterns in Bone Marrow-Derived Mesenchymal Stem Cells of Ovariectomized Rats Treated by Zuogui Pill and Estradiol

作　　者：赵旭[1,2] 刘秋红[2] 许文亚[2] 郝传铮[1] 徐俊伟[1] 胡平[1] 

机构地区：[1]南通大学附属医院,江苏南通226001 [2]苏州市中医医院,江苏苏州215009

出　　处：《辽宁中医杂志》2016年第11期2394-2398,共5页Liaoning Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81102622);南通大学附属医院转化医学基地科研项目(TDFzh201408)

摘　　要：目的:分析不同干预下去卵巢大鼠骨髓间充质干细胞(bone marrow-derived mesenchymal stem cells,BMSCs)多时相差异表达基因(differentially expressed genes,DEGs)及其参与的功能和通路,全面比较左归丸与雌二醇防治绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)基因调控机理之异同。方法:72只大鼠随机均分为假手术组、模型组、雌二醇组和左归丸组。术后两周,雌二醇组和左归丸组分别灌胃给药至术后第4、8和12周末。无菌分离、培养各组BMSCs。表达谱芯片技术检测F2代BMSCs全基因组表达。以SPSS 18.0软件筛选DEGs(阈值:P<0.0.05,差异倍数>2或<0.5),并通过DAVID进行功能与通路富集(阈值:P<0.05)。结果:4周左归丸-模型对比组的DEGs多达99个。左归丸-模型组的DEGs显著富集在细胞增殖、骨架形成、激素刺激、细胞黏附、钙平衡、信号通路、轴突等功能,而左归丸和雌二醇在转运蛋白-细胞膜、细胞增殖、激素刺激等功能调控上存在差异。结论:左归丸可能通过广泛调控BMSCs基因(如Cenpn、Clec4f、Plac1及Ccdc88a)的表达,影响多种功能与通路,最终减少骨量丢失。Objective ： This study aims to investigate the effects of Zuogui Pill on the gene expression in BMSCs （ bone marrow - derived mesenchymal stem cells） of PMOP （ postmenopausal osteoporosis） model rats as well as the underlying mechanism via analyzing DEGs （ differentially expressed genes ） and the corresponding functions and pathways. Besides, the similarities and differences between therapeutic mechanism of Zuogui Pill and estradiol valerate were studied. Methods ： A total of 72 female rats were randomly and equally divided into sham, model, estrogen and Zuogui Pill groups. Estradiol valerate and Zuogui Pill were administered intragastricaXly to rats in estrogen and Zuogui Pill groups, respectively, from 2 weeks post -operation to 4,8 and 12 weeks post - operation. BMSCs of 12 groups （4 × 3 ） were separated and cultivated and microarrays were used to detect the gene expression in F2 generation of BMSCs. The SPSS 18.0 was utilized to screen DEGs （criteria：P 〈 0. 0.05, fold change 〉 2 or 〈 0.5 ） , and functional and pathway enrichment analyses were performed using DAVID （ criteria ： P 〈 0. 0.05 ）. Results ： A total of 99 DEGs were identified in Zuogui Pill -model group （4 weeks） ,which were significantly enriched in functions about cell proliferation, cytoskeleton formation, hormone stimulation, cell adhesion, calcium balance, signaling pathway, and axon. Moreover, Zuogui Pill was different from estrogen in the regulation of translocator - membrane, cell proliferation, hormone stimulation, etc. Concluzion ： Zuogui Pill might affect multiple functions and pathways of BMSCs, and thus inhibiting bone loss via extensively regulating the expressions of multiple genes like Cenpn, Clec4f, Placl and Ccdc88a. In this study, the gene expression regulation and therapeutic mechanism of Chinese and western medicines were investigated as well as their similarities and differences.

关 键 词：绝经后骨质疏松症 骨髓间充质干细胞 左归丸 雌二醇 富集分析 

分 类 号：R285.5[医药卫生—中药学]